PRIORITIZE: Study of Oral Treatments for Hepatitis C

Sponsor

University of Florida (Other)

Overall Status

Completed

CT.gov ID

NCT02786537

Collaborator

Patient-Centered Outcomes Research Institute (Other), Merck Sharp & Dohme LLC (Industry), AbbVie (Industry)

1,275

Enrollment

Locations

Arms

51.1

Duration (Months)

33.6

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase 1 of this study compared the effectiveness of 3 approved DAA (direct-acting antiviral) HCV treatment regimens to learn whether they worked equally well under real-world conditions. Phase 2 of this study began early 2017 with removal of 1 DAA regimen, limiting randomization to just 2 FDA approved DAA regimens. Patients receiving HCV therapy in community and academic clinics were offered the opportunity to consent to be randomly assigned to one of three (phase 1) or one of two (phase 2) regimens and observed for outcomes. Once randomized, all medical care, laboratory testing, and any disease or side effect management were assumed by usual care conditions, and patient-reported outcomes were collected outside clinic in keeping with pragmatic design principles.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: SOF/LDV (sofosbuvir/ledipasvir) Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only) Drug: EBR/GZR (elbasvir/grazoprevir) Drug: Ribavirin	Phase 4

Detailed Description

In Phase 1 of this study, consented patients were randomized to 1 of the following 3 HCV DAA treatments: 1) Harvoni® (SOF/LDV) 2) Viekira Pak™ (PrOD) 3) Zepatier™ (EBR/GZR) with the optional addition of Ribavirin (RBV) and the length of treatment determined by the individual provider.

In Phase 2 of this study, consented patients were randomized to 1 of 2 FDA approved HCV treatments: Harvoni® or Zepatier™. Both Phase 1 and Phase 2 subjects had up to 1 tablespoon of blood drawn for HCV resistance testing and future biorepository testing (following appropriate additional consent). The results of testing determined whether a genotype 1a subject randomized to Zepatier would be provided 12 or 16 wks of Zepatier.

Following enrollment/randomization, participants completed patient reported outcome questionnaires (PROs) via electronic device or telephone. Following baseline/randomization, participants were asked to complete surveys again at Wk 4 of treatment, End of Treatment, 1 and 3 year post treatment. Patients continued standard medical care throughout study. Data was abstracted from test results and medical records throughout treatment and for up to 3 years post treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

1275 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders

Study Start Date :

Jun 1, 2016

Actual Primary Completion Date :

Jun 13, 2019

Actual Study Completion Date :

Sep 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: EBR/GZR (elbasvir/grazoprevir) with RBV Patients received 1 EBR/GZR (elbasvir/grazoprevir) (Zepatier) tablet (50/100mg) once daily for 12 to 16 weeks (provider discretion) with Ribavirin (RBV) 200 mg/tablet, 1-3/day, taken 1-2 times per day (dosage at discretion of provider).	Drug: EBR/GZR (elbasvir/grazoprevir) Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks Other Names: Zepatier Drug: Ribavirin 200 mg pills (1-3 pills, 1-2 times per day) Other Names: RBV
Active Comparator: EBR/GZR (elbasvir/grazoprevir) Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (provider discretion) (without Ribavirin)	Drug: EBR/GZR (elbasvir/grazoprevir) Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks Other Names: Zepatier
Active Comparator: SOF/LDV (sofosbuvir/ledipasvir) with RBV Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) (Harvoni) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (at discretion of provider). RBV taken as 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.	Drug: SOF/LDV (sofosbuvir/ledipasvir) Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) Other Names: Harvoni® (sofosbuvir/ledipasvir) Drug: Ribavirin 200 mg pills (1-3 pills, 1-2 times per day) Other Names: RBV
Active Comparator: SOF/LDV (sofosbuvir/ledipasvir) Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)	Drug: SOF/LDV (sofosbuvir/ledipasvir) Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) Other Names: Harvoni® (sofosbuvir/ledipasvir)
Active Comparator: PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) with RBV (Phase 1 only) Patients received Pr0D (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) orally daily with food for 12 to 24 weeks with RBV (Ribavirin). Ombitasvir/Paritaprevir/Ritonavir (12.5/75/50 mg/tablet) -2 tablets once daily with food for 12 to 24 weeks and 1 dasabuvir tablet (250 mg) twice daily with food for 12 to 24 weeks. RBV (200 mg/pill) 1-3 pills/day, 1-2 times/day (use and dosage at provider discretion). Total daily RBV dosage ranged from 200 to 1200 mg.	Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider) Other Names: Viekira Pak/Viekira
Active Comparator: PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir) Patients received 2 ombitasvir/paritaprevir/ritonavir tablets (12.5/75/50 mg) once daily and 1 dasabuvir (250 mg) tablet twice daily with food for 12 to 24 weeks without Ribavirin (as per provider instructions)	Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider) Other Names: Viekira Pak/Viekira Drug: Ribavirin 200 mg pills (1-3 pills, 1-2 times per day) Other Names: RBV

Outcome Measures

Primary Outcome Measures

Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV [12 weeks post-treatment]
SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider). mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2.
Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation) [12-24 weeks post HCV treatment]
SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2.
Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation [12 weeks post-treatment]
SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only.
Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation) [12 -24 weeks post-treatment]
SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants randomized during Phase 1 only.
Mean Change in Headache-PRO Scores -Phase 1 [Baseline to On-Treatment]
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom.
Mean Change in Headache-EBR/GZR and SOF/LDV [Baseline to On-Treatment]
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Median Change in Headache -Phase 1 [12 weeks (Baseline and Average On-treatment Score)]
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Median Change in Headache-Phase 2 [Baseline -on Treatment (12-16 weeks)]
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Mean Change in Nausea/Vomiting PRO Score -Phase 1 [Baseline to On-Treatment]
Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status.
Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF [Baseline and Average On-Treatment Score]
Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting. Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment. A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Median Change in Nausea PRO Score -Phase 1 [Baseline to end of treatment]
Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV [Baseline- On Treatment (up to 16 weeks)]
Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Mean Change in Fatigue PRO Score -Phase 1 [Baseline to On-treatment]
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV [Baseline and Average On-Treatment Score]
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Median Change in Fatigue -Phase 1 [Baseline to End of Treatment]
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Median Change in Fatigue-Phase 2 [Baseline-On Treatment (up to 16 weeks)]
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Mean Change in HCV- PRO- Phase 1 [Baseline to End of Treatment]
HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.
Median Change in HCV-PRO (Overall Well Being) -Phase 1 [Baseline to End of Treatment]
HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.
Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2 [End of Treatment - Baseline]
HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2.
16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs [12 weeks post treatment]
Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms). Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients.

Secondary Outcome Measures

Treatment Non-Adherence Probability Estimates [12-16 weeks of HCV treatment]
The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being "Non-adherent" if any response was > 1, otherwise they were coded as "Adherent". Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD
Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation [1 year post treatment discontinuation (Early post-tx)]
Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement.
Post-treatment Progression/Regression of Liver Disease-Fib-4 [Baseline to up to 3 years post treatment discontinuation]
Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis.
Change in Functional Status (HCV-PRO) Within Treatment [Treatment start date up to 2 years post-treatment]
HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.
Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF [Treatment start date through treatment completion (up to 24 weeks)]
The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)
HCV SVR Durability -No Cirrhosis [24 weeks post-end of treatment up to 153 weeks]
Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
HCV SVR Durability-Patients With Cirrhosis [Up to 132 weeks post HCV treatment]
Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2 [12 weeks post HCV treatment]
Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

HCV Genotype 1a or 1b
Adult patients (age 18 years or older)
Patients being prescribed HCV treatment who can begin treatment with any of the three HCV treatments being studied (Harvoni (SOF/LDV), Viekira Pak (PrOD) (Phase 1 only), or Zepatier (EBR/GZR))

Exclusion Criteria:

Inability to provide written informed consent
HARVONI® is not a covered drug on benefits formulary
Current or historical evidence of hepatic decompensation (variceal bleeding, hepatic encephalopathy, or ascites)
Child Pugh (CTP) B or C Cirrhosis (documented CTP calculation is required)
Pregnant or breastfeeding women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liver Wellness Center	Little Rock	Arkansas	United States	72205
2	Stanford University	Palo Alto	California	United States	94304
3	UCSD Medical Center	San Diego	California	United States	92103
4	UCSF/Zuckerberg San Francisco General Hospital and Trauma Center	San Francisco	California	United States	94110
5	Univ of California, San Francisco	San Francisco	California	United States	94143
6	Yale University Digestive Diseases	New Haven	Connecticut	United States	06520
7	Georgetown University	Washington	District of Columbia	United States	20007
8	Howard University	Washington	District of Columbia	United States	20060
9	University of Florida	Gainesville	Florida	United States	32610-0272
10	University of Florida, Jacksonville	Jacksonville	Florida	United States	32209
11	University of Miami/Schiff Center for Liver Diseases	Miami	Florida	United States	33136
12	Orlando Immunology Center	Orlando	Florida	United States	32803
13	Internal Medicine Associates of Wellstar Atlanta Medical Center	Atlanta	Georgia	United States	30312
14	Northwestern University	Chicago	Illinois	United States	60611
15	Northwestern University	Chicago	Illinois	United States	60647
16	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
17	John Hopkins University	Lutherville	Maryland	United States	21093
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
19	University of Michigan	Ann Arbor	Michigan	United States	48109
20	University of Minnesota	Minneapolis	Minnesota	United States	55455
21	GI Associates & Endoscopy Center	Flowood	Mississippi	United States	39232
22	Saint Louis University	Saint Louis	Missouri	United States	63104
23	University of Nebraska Medical Ctr	Omaha	Nebraska	United States	68198
24	Southwest CARE Center	Santa Fe	New Mexico	United States	87505
25	Mt. Sinai Beth Israel	New York	New York	United States	10003
26	New York Langone Medical Center	New York	New York	United States	10016
27	Weill Cornell Medical College	New York	New York	United States	10021
28	Columbia University Medical Center	New York	New York	United States	10032
29	Mountain View Medical Center	Valatie	New York	United States	12184
30	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
31	Duke University Medical Center	Durham	North Carolina	United States	27710
32	University of Cincinnati	Cincinnati	Ohio	United States	45267
33	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
34	Research Specialist of Texas	Houston	Texas	United States	77030
35	Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)	Richmond	Virginia	United States	23226
36	Virginia Commonwealth University	Richmond	Virginia	United States	23284
37	Virginia Mason Medical Center	Seattle	Washington	United States	98101
38	University of Washington	Seattle	Washington	United States	98104

Sponsors and Collaborators

University of Florida
Patient-Centered Outcomes Research Institute
Merck Sharp & Dohme LLC
AbbVie

Investigators

Principal Investigator: David R Nelson, MD, University of Florida

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Sep 18, 2018

More Information

Publications

None provided.

Responsible Party:

University of Florida

ClinicalTrials.gov Identifier:

NCT02786537

Other Study ID Numbers:

16-1234
PCORI-1503-27891
IRB201501162

First Posted:

Jun 1, 2016

Last Update Posted:

Dec 6, 2021

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by University of Florida

Hepatitis C

Additional relevant MeSH terms:

Elbasvir-grazoprevir drug combination

Study Results

Participant Flow

Recruitment Details

Participants were consented at 34 US centers Between June 2016 and March 2018. Patients' insurance was screened for inclusion of SOF/LDV on formulary (the HCV regimen not provided by the study). However, following randomization, participants who were unable to obtain SOF/LDV through insurance received 1 of 2 Direct Acting Antiviral (DAA) HCV Treatment regimens 1)EBR/GZR or 2)PrOD during Phase 1 and received EBR/GZR during Phase 2.

Pre-assignment Detail

This study initially (Phase 1) randomized subjects to receive 1 of 3 HCV DAA regimens (EBR/GZR +/- RBV, LDV/SOF +/- RBV, or PrOD +/-RBV). In phase 2 of this study, randomization to PrOD regimen was discontinued and newly enrolled subjects were randomized to either EBR/GZR +/- RBV or LDV/SOF +/- RBV. Efficacy data was analyzed via original 'randomization' and as subjects were 'actually treated (regimen actually received)' while safety analysis was evaluated by actual treatment received.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD/RBV(Phase 1 Only)	PrOD (Phase 1 Only)
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) (Zepatier™) orally once daily with RBV for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food and with RBV: Ribavirin (200 mg pill) 1-3 pills/day, once or twice daily. Total daily dosage ranged from 200 to 1200 mg.	Patients received EBR/GZR (elbasvir/grazoprevir) (Zepatier™) orally once daily (without RBV) for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks. Duration of treatment according to HCV treatment provider.	Patients received SOF/LDV(sofosbuvir/ledipasvir) (Harvoni®) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV/sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) 1 tablet daily for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) RBV (200 mg pill): 1-3 pills, once or twice daily (dosing per discretion of HCV provider). Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) (Harvoni®) orally once daily with or without food 12 to 24 weeks SOF/LDV: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider)	PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir (Viekira) once or twice daily with a meal for 12 to 24 weeks + RBV (provider discretion). Randomization to PrOD discontinued January 2017. ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks with food (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg twice daily for 12 to 24 weeks with a meal RBV: Ribavirin 200 to 600 mg once or twice daily	Randomization to Prod discontinued January 2017 (defining end of Phase 1) PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir: 250 mg daily for 12 to 24 weeks
Period Title: As Randomized
STARTED	56	644	15	413	99	48
COMPLETED	50	582	15	378	87	41
NOT COMPLETED	6	62	0	35	12	7
Period Title: As Randomized
STARTED	56	664	15	394	99	47
COMPLETED	50	602	15	359	87	40
NOT COMPLETED	6	62	0	35	12	7

Baseline Characteristics

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PROD With RBV (Phase 1 Only)	PROD (Phase 1 Only)	Total
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily with RBV for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir 50/100mg tablet) once daily with or without food with or without RBV for 12 to 16 weeks (with RBV)	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir 50/100mg tablet): 1 tablet once daily with or without food with or without RBV for 12 to 16 weeks (without RBV)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks with Ribavirin (RBV) (treatment duration and use of ribavirin is per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (per discretion of provider) SOF/LDV: Sofosbuvir/Ledipasvir (400/90 mg tablet ) 1 tablet orally once daily for approximately 12 to 24 weeks	Phase 1 only - Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks +/- RBV (provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg daily for 12 to 24 weeks	Phase 1 only - Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks Dasabuvir: 250 mg daily for 12 to 24 weeks	Total of all reporting groups
Overall Participants	56	644	15	413	99	48	1275
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	44 78.6%	547 84.9%	8 53.3%	319 77.2%	86 86.9%	35 72.9%	1039 81.5%
>=65 years	12 21.4%	97 15.1%	7 46.7%	94 22.8%	13 13.1%	13 27.1%	236 18.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.1 (11.0)	53.3 (12.2)	61.1 (6.6)	56.2 (11.1)	54.5 (11.3)	59.9 (10.1)	54.7 (11.8)
Sex: Female, Male (Count of Participants)
Female	13 23.2%	280 43.5%	6 40%	157 38%	35 35.4%	16 33.3%	507 39.8%
Male	43 76.8%	364 56.5%	9 60%	256 62%	64 64.6%	32 66.7%	768 60.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 8.9%	44 6.8%	0 0%	26 6.3%	5 5.1%	1 2.1%	81 6.4%
Not Hispanic or Latino	51 91.1%	586 91%	14 93.3%	375 90.8%	90 90.9%	45 93.8%	1161 91.1%
Unknown or Not Reported	0 0%	14 2.2%	1 6.7%	12 2.9%	4 4%	2 4.2%	33 2.6%
Region of Enrollment (participants) [Number]
United States	56 100%	644 100%	15 100%	413 100%	99 100%	48 100%	1275 100%
HCV RNA (10^6 units IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^6 units IU/mL]	4.9 (6.7)	3.1 (4.9)	5.9 (4.7)	3.5 (4.4)	3.5 (3.8)	3.7 (4.2)	3.4 (4.7)

Outcome Measures

1. Primary Outcome

Title	Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV
Description	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider). mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2.
Time Frame	12 weeks post-treatment

Outcome Measure Data

Analysis Population Description
mITT with imputation, Missing SVR data = Failure. Numbers represent participants according to arm randomized (Period 1). Population excludes participants who did not start any HCV treatment.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZV (50/100mg) tablet: once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	56	644	15	413
Count of Participants [Participants]	40 71.4%	516 80.1%	14 93.3%	335 81.1%

2. Primary Outcome

Title	Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
Description	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2.
Time Frame	12-24 weeks post HCV treatment

Outcome Measure Data

Analysis Population Description
All mITT without imputation (missing data excluded). Includes only number of participants for whom SVR12 data is available and based on study drug as randomized (Period 1). Participants for whom SVR 12 is not available are excluded from this table.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received elbasvir/grazoprevir (EBR/GZR) tablet orally once daily with or without Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks Ribavirin (RBV) (200 mg pill)- 1-3 pills orally once or twice daily (dosage at provider discretion)	Patients received elbasvir/grazoprevir (EBR/GZR) once daily for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (treatment duration per discretion of provider) sofosbuvir/ledipasvir: 1 Sofosbuvir/Ledipasvir (400/90 mg) tablet once daily with or without food for approximately 12 to 24 weeks Ribavirin (200 mg pill): 200 to 600 mg once or twice daily (treatment duration and dosage of ribavirin as per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily for 12 to 24 weeks (treatment duration as per discretion of HCV treatment provider) SOF/LDV (400/90 MG TABLET): 1 tablet orally once daily for 12 to 24 weeks
Measure Participants	46	540	15	344
Count of Participants [Participants]	40 71.4%	516 80.1%	14 93.3%	335 81.1%

3. Primary Outcome

Title	Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation
Description	SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only.
Time Frame	12 weeks post-treatment

Outcome Measure Data

Analysis Population Description
mITT with imputation, Missing SVR data =failure. Numbers represent participants according to arm randomized (period 1). Population excludes participants who did not start any HCV treatment.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks
Measure Participants	13	134	6	105	99	48
Count of Participants [Participants]	9 16.1%	108 16.8%	6 40%	88 21.3%	77 77.8%	42 87.5%

4. Primary Outcome

Title	Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
Description	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants randomized during Phase 1 only.
Time Frame	12 -24 weeks post-treatment

Outcome Measure Data

Analysis Population Description
Participants analyzed based on HCV treatment as assigned by randomization.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD (Phase 1 Only)
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR: Elbasvir/grazoprevir (50/100mg) 1 tablet once daily with or without food with or without RBV for 12 to 16 weeks Ribavirin at dosages ranging from 200mg to 600 mg daily (or twice daily) can be added to HCV DAA treatment regimen at discretion of HCV treatment provider	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion) EBR/GZR: 1 Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) tablet orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV: At discretion of provider, 200 mg pill, 1-3 pills/day, 1-2 times/day (daily dosing ranging from 200mg to 1200 mg daily) added to HCV treatment regimen	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (Sofosbuvir/Ledipasvir 400/90 mg tablet): 1 tablet daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)	Patients received PrOD (ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily) for 12 to 24 weeks with Ribavirin (RBV) (use and dosage at provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet ) 2 tablets daily for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 500 mg tablet once or twice daily (morning and evening) RBV: At discretion of provider, 200 mg pill, 1-3 pills/day, 1-2 times/day (daily dosing ranging from 200mg to 1200 mg daily) added to HCV treatment regimen	Patients received ProD (ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily) for 12 to 24 weeks without Ribavirin (at provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg tablet twice daily for 12 to 24 weeks
Measure Participants	10	113	6	92	80	42
Count of Participants [Participants]	9 16.1%	108 16.8%	6 40%	88 21.3%	77 77.8%	42 87.5%

5. Primary Outcome

Title	Mean Change in Headache-PRO Scores -Phase 1
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom.
Time Frame	Baseline to On-Treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who completed a baseline and on-treatment PRO and as treated (Period 2) during Phase 1 only.

Arm/Group Title	EBR/GZR With Ribavirin (RBV)	EBR/GZR Regimen	SOF/LDV With RBV	SOF/LDV	PrOD With RBV Regimen	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily withRBV (at discretion of provider) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg - 1 tablet once daily with or without food for 12 to 16 weeks RBV: Ribavirin (200 mg pills) 1-3 pills/day, 1-2 times/day (Total dosage 200-1200 mg day)	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg - 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg pill): 1-3 pills once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	9	84	5	61	62	28
Mean (Standard Deviation) [units on a scale]	0.0 (1.4)	-0.8 (3.5)	-0.7 (5.0)	-0.5 (4.8)	-0.2 (4.7)	-2.2 (4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	PROD vs. SOF/LDV based regimens as reported in PRO (ALL PATIENTS WHO STARTED TREATMENT BY ARM AS TREATED), population limited to as randomization date of the last PrOD patient start date - RBV FREE REGIMENS
	Type of Statistical Test	Superiority
	Comments	Superiority test derived by comparing whether the 95% CI includes zero.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95% -3.6 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, PrOD
	Comments	RBV free EBR/GZR regimen compared to PrOD in consideration that RBV usage was determined by provider and not study randomization.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% -0.4 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method. CI for median derived from PROC QUANTREG.

6. Primary Outcome

Title	Mean Change in Headache-EBR/GZR and SOF/LDV
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame	Baseline to On-Treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to participants who completed both baseline and end of treatment PRO

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	40	403	10	222
Mean (Standard Deviation) [units on a scale]	-0.8 (3.1)	-0.7 (4.4)	0.4 (6.2)	-0.8 (5.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis based on RBV free EBR/GZR regimen vs SOF/LDV (all patients who started treatment by arm as treated)
	Type of Statistical Test	Superiority
	Comments	Superiority test completed by comparing whether the 95% CI includes zero.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95% -0.6 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

7. Primary Outcome

Title	Median Change in Headache -Phase 1
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame	12 weeks (Baseline and Average On-treatment Score)

Outcome Measure Data

Analysis Population Description
Analysis limited to patients randomized up to last patient randomized to PrOD and participants who completed baseline and on-treatment survey.

Arm/Group Title	EBR/GZR (Elbasvir/Grazoprevir) With RBV	EBR/GZR (Elbasvir/Grazoprevir)	SOF/LDV (Sofosbuvir/Ledipasvir) With RBV	SOF/LDV (Sofosbuvir/Ledipasvir)	PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) With RBV (Phase 1 Only)	PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir)
Arm/Group Description	Patients received 1 EBR/GZR (elbasvir/grazoprevir) (Zepatier) tablet (50/100mg) once daily for 12 to 16 weeks (provider discretion) with Ribavirin (RBV) EBR/GZR (elbasvir/grazoprevir): Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks Ribavirin: 200 mg/tablet, 1-3/day, taken 1-2 times per day (dosage at discretion of provider).	Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (treatment duration per provider discretion) EBR/GZR (elbasvir/grazoprevir): Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food for 12 to 16 weeks	Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) (Harvoni) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (duration and usage of RBV at discretion of provider). SOF/LDV (sofosbuvir/ledipasvir): Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks Ribavirin (RBV): 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.	Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (sofosbuvir/ledipasvir): Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration at discretion of HCV provider)	Patients received Pr0D (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) orally daily with food for 12 to 24 weeks with RBV (Ribavirin). Ombitasvir/Paritaprevir/Ritonavir (12.5/75/50 mg/tablet) -2 tablets once daily with food for 12 to 24 weeks and 1 dasabuvir tablet (250 mg) twice daily with food for 12 to 24 weeks. RBV (200 mg/pill) 1-3 pills/day, 1-2 times/day (use and dosage at provider discretion). Total daily RBV dosage ranged from 200 to 1200 mg.	Patients received 2 ombitasvir/paritaprevir/ritonavir tablets (12.5/75/50 mg) once daily and 1 dasabuvir (250 mg) tablet twice daily with food for 12 to 24 weeks without Ribavirin (as per provider instructions) PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only): Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider)
Measure Participants	9	84	5	61	62	28
Median (Full Range) [units on a scale]	0.0	0.0	-2.0	-1.0	0.0	-1.0

8. Primary Outcome

Title	Median Change in Headache-Phase 2
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame	Baseline -on Treatment (12-16 weeks)

Outcome Measure Data

Analysis Population Description
Analysis limited to patients randomized to EBR/GZR regimen or SOF/LDV regimen and participants who completed both baseline and on treatment survey.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks. EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration per investigator's discretion) EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without RBV SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	40	403	10	222
Median (Full Range) [units on a scale]	-1.0	0.0	0.5	-0.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis of EBR/GZR vs. SOF/LDV irrespective of RBV usage in consideration that RBV usage was determined by provider and not study randomization.
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95% 0.0 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparisons between regimens can be viewed as superiority test, by comparing whether the 95% CI includes zero

9. Primary Outcome

Title	Mean Change in Nausea/Vomiting PRO Score -Phase 1
Description	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status.
Time Frame	Baseline to On-Treatment

Outcome Measure Data

Analysis Population Description
Analysis is limited to patients who completed at least one baseline and one end of treatment PRO survey during Phase 1 (end date corresponds to last PrOD patient start date)

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	8	79	5	58	59	25
Mean (Standard Deviation) [units on a scale]	1.3 (5.0)	-1.4 (8.8)	-3.9 (4.0)	-0.7 (10.7)	2.5 (8.6)	0.7 (12.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	Analysis based on RBV free SOF/LDV vs. PrOD in consideration that RBV usage was determined by provider and not study randomization and limited RBV sample size.
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% -4.2 to 7.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	RBV free PrOD vs. SOF/LDV regimens (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date)
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% -4.2 to 7.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

10. Primary Outcome

Title	Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF
Description	Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting. Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment. A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Time Frame	Baseline and Average On-Treatment Score

Outcome Measure Data

Analysis Population Description
Patients with Baseline PROMIS Nausea/vomiting score who started treatment by arm as treated and completed baseline and on-treatment survey.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage 200 mg- 1200 mg.	Patients received 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	37	381	9	202
Mean (Standard Deviation) [units on a scale]	-0.3 (8.3)	-0.6 (8.7)	-1.6 (4.7)	-0.4 (9.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	RBV free EBR/GZR vs. SOF/LDV (all patients who started treatment by arm as treated)
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95% -1.6 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

11. Primary Outcome

Title	Median Change in Nausea PRO Score -Phase 1
Description	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Time Frame	Baseline to end of treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who completed baseline and on treatment Nausea short form during Phase 1 (up to last PrOD randomized) as treated.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration as per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	8	79	5	58	59	25
Median (Full Range) [units on a scale]	0.4	0.0	-6.1	0.0	0.0	0.0

12. Primary Outcome

Title	Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV
Description	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Time Frame	Baseline- On Treatment (up to 16 weeks)

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZV (50/100mg) tablet: once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	37	381	9	202
Median (Full Range) [score on a scale]	0.0	0.0	0.0	0.0

13. Primary Outcome

Title	Mean Change in Fatigue PRO Score -Phase 1
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline to On-treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who completed baseline and at least one on-treatment Fatigue PRO survey during phase 1 as treated.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider). Total daily dosage ranged from 200 to 1200 mg daily.	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	Patients received PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets, 1-2 times per day, daily for 12 to 24 weeks (dosage and duration at discretion of provider)	Patients received PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	9	78	5	59	59	27
Mean (Standard Deviation) [units on a scale]	1.5 (7.7)	-1.2 (9.2)	-7.2 (10.2)	-2.0 (7.9)	-1.9 (11.3)	-3.0 (7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, PrOD
	Comments	RBV free EBR/GZR vs. PrOD regimens as reported in PRO (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date). Analysis limited to RBV free regimen in consideration RBV usage determined by provider and not study randomization.
	Type of Statistical Test	Superiority
	Comments	Superiority test based on whether the 95% CI includes zero

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95% -1.9 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	RBV free SOF/LDV vs. PrOD regimens as reported in PRO (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date)
	Type of Statistical Test	Superiority
	Comments	Superiority test based on whether the 95% CI includes zero

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95% -4.6 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

14. Primary Outcome

Title	Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline and Average On-Treatment Score

Outcome Measure Data

Analysis Population Description
Patients with Baseline PROMIS Fatigue score who started treatment by arm as treated (Period 2)

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 - 3 tablets,1-2 times per day, daily for 12 to 16 weeks (dosage and duration per discretion of provider).	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion)	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food, daily for 12 - 24 weeks (use of RBV and dosage at discretion of provider)	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	38	398	10	213
Mean (Standard Deviation) [score on a scale]	-1.0 (7.7)	-2.1 (9.1)	-3.7 (8.3)	-2.2 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis limited to RBV free regimens in consideration that RBV usage determined by provider and not study randomization. All patients who started treatment by arm as treated.
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on presence of zero in 95% CI.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95% -1.4 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method

15. Primary Outcome

Title	Median Change in Fatigue -Phase 1
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline to End of Treatment

Outcome Measure Data

Analysis Population Description
Analysis is limited to patients who completed baseline and on-treatment fatigue PRO during Phase 1 (last PrOD patient started). Safety profiles of the evaluated regimens in PRIORITIZE are by actual treatment received.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR Regimen	SOF/LDV With RBV	SOF/LDV	PrOD Regimen With RBV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider). Total daily dosage ranged from 200 to 1200 mg daily.	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	9	78	5	59	59	27
Median (Full Range) [units on a scale]	2.2	-0.9	-10.2	-3.4	-0.2	-4.1

16. Primary Outcome

Title	Median Change in Fatigue-Phase 2
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline-On Treatment (up to 16 weeks)

Outcome Measure Data

Analysis Population Description
Analysis limited to Period 2 -as treated, participants who completed baseline and on-treatment surveys.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received elbasvir/grazoprevir (EBR/GZR) tablet orally once daily with or without Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks Ribavirin (RBV) (200 mg tablet)- 1-3 tablets orally, once or twice daily (dosage at provider discretion). Total daily dosage 200 -1200 mg.	Patients received elbasvir/grazoprevir (EBR/GZR) once daily for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (treatment duration per discretion of provider) sofosbuvir/ledipasvir: 1 Sofosbuvir/Ledipasvir (400/90 mg) tablet once daily with or without food for approximately 12 to 24 weeks Ribavirin (200 mg tablet): 1-3 tablets, once or twice daily (treatment duration and dosage of ribavirin as per discretion of HCV provider).	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily for 12 to 24 weeks (treatment duration as per discretion of HCV treatment provider) SOF/LDV (400/90 MG TABLET): 1 tablet orally once daily for 12 to 24 weeks
Measure Participants	38	398	10	213
Median (Full Range) [units on a scale]	-1.3	-1.2	-2.4	-1.4

17. Primary Outcome

Title	Mean Change in HCV- PRO- Phase 1
Description	HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4N)100, where N is the number of questions answered.
Time Frame	Baseline to End of Treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who completed baseline and at least one on treatment Fatigue Short form. Evaluation is based on actual HCV regimen received.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dose ranging from 200 mg to 1200 mg.	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets, once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider).	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	9	84	5	61	61	29
Mean (Standard Deviation) [units on a scale]	-0.9 (12.4)	5.6 (14.0)	2.5 (7.1)	6.9 (16.9)	3.2 (22.8)	9.9 (12.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, PrOD
	Comments	Analysis based on RBV free regimens -all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date.
	Type of Statistical Test	Superiority
	Comments	Superiority test determined by comparing presence of zero in CI.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95% -9.9 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	RBV free regimens as reported in PRO (all patients who started treatment by arm as treated, population limited to as randomization date of the last PrOD patient start date)
	Type of Statistical Test	Superiority
	Comments	Superiority comparison by viewing presence of zero in CI.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95% -3.4 to 9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Primary Outcome

Title	Median Change in HCV-PRO (Overall Well Being) -Phase 1
Description	HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4N)100, where N is the number of questions answered.
Time Frame	Baseline to End of Treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who completed baseline and at least one survey while on treatment up to end of treatment. Evaluation was based on actual regimen received versus regimen to which patient was randomized.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description	Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider)	Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration as HCV provider discretion)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranging from 200 - 1200 mg.	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Measure Participants	9	84	5	61	61	29
Median (Full Range) [score on a scale]	0.0	4.3	4.7	4.7	3.1	8.6

19. Primary Outcome

Title	Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2
Description	HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4N)100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2.
Time Frame	End of Treatment - Baseline

Outcome Measure Data

Analysis Population Description
Patients with completed Baseline and End of Treatment HCV-PRO survey who started treatment by arm as treated (Period 2)

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dose ranging from 200 mg to 1200 mg.	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Measure Participants	40	413	10	226
Mean (Standard Deviation) [score on a scale]	3.2 (18.6)	6.1 (15.7)	6.3 (10.7)	6.8 (18.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis based on RBV free regimens in consideration that RBV usage was determined by provider and not study randomization. Population includes patients who started treatment by arm as treated.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95% -3.6 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

20. Primary Outcome

Title	16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs
Description	Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms). Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients.
Time Frame	12 weeks post treatment

Outcome Measure Data

Analysis Population Description
All Genotype 1a patients who started treatment by arm randomized (Elbasvir/Grazobevir) with Baseline RAS at any location (28, 30, 31, or 93)

Arm/Group Title	EBR/GZR With RBV-16 Weeks
Arm/Group Description	Subjects received EBR/GZR (elbasvir/grazoprevir) once daily with Ribavirin (RBV) for 16 weeks (as per provider discretion) EBR/GZR: Elbasvir/grazoprevir (50/100mg tablet) 1 tablet once daily with or without food RBV (200 mg tablet): 1-3 tablets once or twice daily for 16 weeks (dosage and duration at discretion of provider). Total dosage ranging from 200 mg to 1200 mg daily.
Measure Participants	38
Count of Participants [Participants]	34 60.7%

21. Secondary Outcome

Title	Treatment Non-Adherence Probability Estimates
Description	The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being "Non-adherent" if any response was > 1, otherwise they were coded as "Adherent". Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD
Time Frame	12-16 weeks of HCV treatment

Outcome Measure Data

Analysis Population Description
Analysis is limited to participants to patients who started treatment prior to January 2017 (last day patient started on PrOD treatment)

Arm/Group Title	EBR/GZR	SOF/LDV	PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with or without RBV for 12 to 16 weeks (provider discretion) EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranging from 200-1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with or without Ribavirin ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)
Measure Participants	151	108	146
Number (95% Confidence Interval) [percentage of patients]	23	19	26

22. Secondary Outcome

Title	Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation
Description	Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement.
Time Frame	1 year post treatment discontinuation (Early post-tx)

Outcome Measure Data

Analysis Population Description
Analysis includes all patients who started treatment on either EBR/GZR or SOF/LDV regimen and is limited to patients who completed surveys. Analysis does not decipher between RBV usage given RBV usage was based on HCV provider selection and not study randomization

Arm/Group Title	EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description	Patients received elbasvir/grazoprevir tablet tablet once daily with or without RBV (at discretion of provider) for 12 to 16 weeks (provider discretion) elbasvir/grazoprevir: Elbasvir/grazoprevir (50/100mg) tablet once daily with food and with RBV: Ribavirin (200 mg/pill) 1-3 pills/day, 1-2 times/day. Total daily dosage ranged from 200 to 1200 mg.	Patients received 1 tablet SOF/LDV(sofosbuvir/ledipasvir) orally once daily with or without ribavirin (RBV) (per discretion of provider) with or without food 12 to 24 weeks SOF/LDV/sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) RBV: Ribavirin (200mg pill) 1-3 pills, once or twice/day -dosage at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.
Measure Participants	507	286
Nausea	0.00	-4.99
Belly Pain	-0.82	-6.47
Diarrhea	-1.12	-5.77
Fatigue	-2.08	-7.59
Sleep Disturbance	0.65	-1.72
Cognitive Impairment	-0.54	-4.48
HCV-PRO	8.02	9.90

23. Secondary Outcome

Title	Post-treatment Progression/Regression of Liver Disease-Fib-4
Description	Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis.
Time Frame	Baseline to up to 3 years post treatment discontinuation

Outcome Measure Data

Analysis Population Description

Population analyzed limited to cirrhotic patients who had two separate FIB-4 values collected as part of standard care and achieved SVR (defined as undetectable HCV 24 weeks post treatment). Given pragmatic trial design, availability of fibrosis markers is limited thereby restricting analysis (substantially limited sample size) to difference in fibrosis markers following SVR with any HCV treatment used in study.

Arm/Group Title	EBR/GZR, SOF/LDV or PrOD Based HCV Treatment
Arm/Group Description	Elbasvir/grazoprevir (EBR/GZR): (50/100mg) tablet once daily with food for 12 to 16 weeks with or without RBV (Ribavirin usage as per provider discretion). Sofosbuvir/ledipasvir (SOF/LDV)/ (400/90 mg) 1 tablet once daily for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) with or without RBV (RBV usage as per provider discretion): PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks + RBV (provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg daily for 12 to 24 weeks RBV: Ribavirin 200 to 600 mg once or twice daily RBV (Ribavirin)- 200mg pill, 1-3 pills/day once or twice daily (use and dosing per discretion of HCV provider).
Measure Participants	108
Median (Full Range) [score on a scale]	-1.36

24. Secondary Outcome

Title	Change in Functional Status (HCV-PRO) Within Treatment
Description	HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement. Total score = (SUM-N)/(4N)100, where N is the number of questions answered.
Time Frame	Treatment start date up to 2 years post-treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who completed HCV-PRO assessments during post-treatment. For this safety analysis, regimen is based on treatment received versus treatment to which patient was randomized. Arms with and without RBV are combined in consideration that usage of RBV was decided by HCV provider and not part of study randomization.

Arm/Group Title	EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description	Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Subjects will take 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)
Measure Participants	498	295
9 months post treatment	8.02	9.90
20 months post treatment	9.87	11.54

25. Secondary Outcome

Title	Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF
Description	The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)
Time Frame	Treatment start date through treatment completion (up to 24 weeks)

Outcome Measure Data

Analysis Population Description
As randomized and treated population during Phase 1 and 2 (See Period 1). Analysis based on HCV DAA regimen randomization per study. Differentiation between RBV usage was not included in analysis given that RBV was not part of study randomization but rather decided by HCV provider.

Arm/Group Title	EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg pill): 1 to 3 pill once or twice daily (dosage and duration per discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg pill: 1 to 3 pills once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.
Measure Participants	700	428
Count of Participants [Participants]	12 21.4%	4 0.6%

26. Secondary Outcome

Title	HCV SVR Durability -No Cirrhosis
Description	Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Time Frame	24 weeks post-end of treatment up to 153 weeks

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who have HCV RNA result at least 24 weeks after end of treatment regimen as per period 1 (As randomized).

Arm/Group Title	EBR/GZR	EBR/GZR With Ribavirin	SOF/LDV	SOF/LDV With RBV	PrOD	PrOD With RBV
Arm/Group Description	Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZV (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)
Measure Participants	255	17	146	2	14	36
Count of Participants [Participants]	255 455.4%	17 2.6%	146 973.3%	2 0.5%	14 14.1%	36 75%

27. Secondary Outcome

Title	HCV SVR Durability-Patients With Cirrhosis
Description	Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Time Frame	Up to 132 weeks post HCV treatment

Outcome Measure Data

Analysis Population Description
Analysis limited to patients who had HCV viral load result at least 24 weeks after treatment and analyzed as per randomized (Period 1)

Arm/Group Title	EBR/GZR	EBR/GZR With RBV	SOF/LDV	SOF/LDV With RBV	PrOD	PrOD With RBV
Arm/Group Description	Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (Ribavirin) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)
Measure Participants	43	7	35	7	6	7
Count of Participants [Participants]	43 76.8%	7 1.1%	35 233.3%	7 1.7%	6 6.1%	7 14.6%

28. Secondary Outcome

Title	Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2
Description	Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen
Time Frame	12 weeks post HCV treatment

Outcome Measure Data

Analysis Population Description
Analysis is based on as assigned by randomization and patients with available RAS data. Exploratory RAS analysis is grouped by DAA regimen with or without RBV given 1)RBV usage was decided by HCV provider and not part of study randomization and small sample size (limited number of RAS in regimens with RBV)

Arm/Group Title	EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (usage, dosage and duration per discretion of provider) (Total dosage ranging from 200 mg to 1200 mg daily)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)
Measure Participants	560	337
With NS5a RAS	47 83.9%	42 6.5%
Without NS5a RAS	485 866.1%	286 44.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR With RBV, EBR/GZR
	Comments
	Type of Statistical Test	Equivalence
	Comments	Pre-specified equivalence range +/-5%

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95% -15.3 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
Time Frame	28 weeks. Adverse events collected up until final viral outcome is determined (approximately 12 weeks after HCV treatment completion).
Adverse Event Reporting Description	An adverse event (AE) is any untoward medical occurrence abstracted from the submitted patient medical records. In order to evaluate the safety profiles of the evaluated regimens, all safety analyses were performed based on 'actual treatment received' (as described in Period 2) rather than treatment to which subject was 'randomized'

Arm/Group Title	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) tablet once daily without RBV for 12 to 16 weeks (provider discretion) EBR/GZR: Elbasvir/grazoprevir (50/100mg tablet) 1 tablet once daily with or without food		Patients received EBR/GZR (elbasvir/grazoprevir tablet) tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food with RBV (200 to 600 mg once or twice daily) for 12 to 16 weeks		Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (Sofosbuvir/Ledipasvir) (400/90 mg tablet) 1 tablet taken daily for approximately 12 to 24 weeks with RBV (Ribavirin) 200 mg: 1-3 pills, one to two times daily (dosage at discretion of HCV provider). Total daily dosage ranged fro 200 to 1200 mg.		Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks (treatment duration per discretion of provider) SOF/LDV (Sofosbuvir/Ledipasvir )(400/90 mg tablet) 1 tablet orally taken daily for approximately 12 to 24 weeks		PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) (treatment at duration provider discretion) ombitasvir/paritaprevir/ritonavir: 2 tablets orally once daily (12.5/75/50mg) for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet orally once or twice daily for 12 to 24 weeks Ribavirin (200 mg pill): 200 to 600 mg once or twice daily (dosage at provider discretion). Total daily dosage ranged from 200 to 1200 mg.		Patients received PrOD orally (ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV) (provider discretion) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg): 2 tablets taken once orally daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/664 (0.9%)		0/56 (0%)		0/15 (0%)		4/394 (1%)		1/99 (1%)		0/47 (0%)
Serious Adverse Events
	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/664 (4.5%)		2/56 (3.6%)		0/15 (0%)		6/394 (1.5%)		5/99 (5.1%)		0/47 (0%)
Cardiac disorders
Chest Pain	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	1/99 (1%)	1	0/47 (0%)	0
Gastrointestinal disorders
Abdominal Pain	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Femoral hernia, obstructive	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Gastric ulcer perforation	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Gastrointestinal haemorrhage	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Small intestinal obstruction	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
General disorders
Drug Withdrawal Syndrome	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Immune system disorders
Hypersensitivity	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Infections and infestations
Cellulitis	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Gastroenteritis viral	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Hepatitis B	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Osteomyelitis	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	1/99 (1%)	1	0/47 (0%)	0
Pneumonia	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	3/394 (0.8%)	3	0/99 (0%)	0	0/47 (0%)	0
Injury, poisoning and procedural complications
Fall	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Gun shot wound	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Hip fracture	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Overdose	2/664 (0.3%)	2	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	1/99 (1%)	1	0/47 (0%)	0
Road traffic accident	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Thermal burn	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Toxicity to various agents	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Metabolism and nutrition disorders
Gout	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Pain in Extremity	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma	0/664 (0%)	0	1/56 (1.8%)	1	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Papillary thyroid cancer	0/664 (0%)	0	1/56 (1.8%)	1	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Nervous system disorders
Adjustment Disorder	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Cerebrovascular Accident	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Haemorrhagic stroke	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Neuropathy peripheral	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Spinal Hematoma	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Syncope	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	1/99 (1%)	1	0/47 (0%)	0
Psychiatric disorders
Alcohol withdrawal Syndrome	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Completed Suicide	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	1/99 (1%)	1	0/47 (0%)	0
Drug Abuse	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	1/99 (1%)	1	0/47 (0%)	0
Mania	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Mental status change	2/664 (0.3%)	2	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Self-injurious ideation	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Renal and urinary disorders
Renal failure acute	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	2/664 (0.3%)	2	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Dyspnoea	2/664 (0.3%)	2	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Respiratory failure	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Surgical and medical procedures
Drug Detoxification	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Vascular disorders
Arteriovenous fistula	1/664 (0.2%)	1	0/56 (0%)	0	0/15 (0%)	0	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Deep Vein Thrombosis	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Peripheral ischaemia	0/664 (0%)	0	0/56 (0%)	0	0/15 (0%)	0	1/394 (0.3%)	1	0/99 (0%)	0	0/47 (0%)	0
Other (Not Including Serious) Adverse Events
	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	298/664 (44.9%)		46/56 (82.1%)		8/15 (53.3%)		184/394 (46.7%)		74/99 (74.7%)		32/47 (68.1%)
Blood and lymphatic system disorders
Anaemia	2/664 (0.3%)	2	17/56 (30.4%)	17	2/15 (13.3%)	2	0/394 (0%)	0	20/99 (20.2%)	20	0/47 (0%)	0
Cardiac disorders
Chest Pain	10/664 (1.5%)	10	1/56 (1.8%)	1	1/15 (6.7%)	1	9/394 (2.3%)	9	3/99 (3%)	3	0/47 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	7/664 (1.1%)	7	1/56 (1.8%)	1	1/15 (6.7%)	1	2/394 (0.5%)	2	3/99 (3%)	3	0/47 (0%)	0
Nausea	54/664 (8.1%)	54	12/56 (21.4%)	12	3/15 (20%)	3	34/394 (8.6%)	34	23/99 (23.2%)	23	5/47 (10.6%)	5
Diarrhoea	45/664 (6.8%)	45	3/56 (5.4%)	3	2/15 (13.3%)	2	19/394 (4.8%)	19	5/99 (5.1%)	5	3/47 (6.4%)	3
Abdominal Pain	11/664 (1.7%)	11	5/56 (8.9%)	5	1/15 (6.7%)	1	11/394 (2.8%)	11	3/99 (3%)	3	0/47 (0%)	0
Constipation	16/664 (2.4%)	16	5/56 (8.9%)	5	0/15 (0%)	0	12/394 (3%)	12	2/99 (2%)	2	2/47 (4.3%)	2
Dyspepsia	5/664 (0.8%)	5	4/56 (7.1%)	4	1/15 (6.7%)	1	3/394 (0.8%)	3	0/99 (0%)	0	2/47 (4.3%)	2
Vomiting	13/664 (2%)	13	3/56 (5.4%)	3	0/15 (0%)	0	13/394 (3.3%)	13	8/99 (8.1%)	8	1/47 (2.1%)	1
Abdominal Pain Upper	8/664 (1.2%)	8	2/56 (3.6%)	2	1/15 (6.7%)	1	9/394 (2.3%)	9	1/99 (1%)	1	1/47 (2.1%)	1
Decreased Appetite	9/664 (1.4%)	9	2/56 (3.6%)	2	1/15 (6.7%)	1	5/394 (1.3%)	5	3/99 (3%)	3	2/47 (4.3%)	2
Hepatobiliary disorders
Hyperbilirubinaemia	0/664 (0%)	0	3/56 (5.4%)	3	0/15 (0%)	0	0/394 (0%)	0	1/99 (1%)	1	0/47 (0%)	0
Cholelithiasis	0/664 (0%)	0	0/56 (0%)	0	1/15 (6.7%)	1	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Infections and infestations
Influenza like illness	18/664 (2.7%)	18	3/56 (5.4%)	3	0/15 (0%)	0	7/394 (1.8%)	7	2/99 (2%)	2	0/47 (0%)	0
Injury, poisoning and procedural complications
Fall	3/664 (0.5%)	3	0/56 (0%)	0	1/15 (6.7%)	1	3/394 (0.8%)	3	0/99 (0%)	0	0/47 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	15/664 (2.3%)	15	3/56 (5.4%)	3	0/15 (0%)	0	12/394 (3%)	12	0/99 (0%)	0	0/47 (0%)	0
Arthralgia	17/664 (2.6%)	17	1/56 (1.8%)	1	1/15 (6.7%)	1	13/394 (3.3%)	13	4/99 (4%)	4	0/47 (0%)	0
Musculoskeletal Pain	2/664 (0.3%)	2	1/56 (1.8%)	1	1/15 (6.7%)	1	3/394 (0.8%)	3	0/99 (0%)	0	0/47 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	0/664 (0%)	0	0/56 (0%)	0	1/15 (6.7%)	1	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Nervous system disorders
Dizziness	15/664 (2.3%)	15	7/56 (12.5%)	7	0/15 (0%)	0	11/394 (2.8%)	11	3/99 (3%)	3	1/47 (2.1%)	1
Fatigue	105/664 (15.8%)	105	18/56 (32.1%)	18	5/15 (33.3%)	5	82/394 (20.8%)	82	35/99 (35.4%)	35	5/47 (10.6%)	5
Headache	94/664 (14.2%)	94	12/56 (21.4%)	12	1/15 (6.7%)	1	68/394 (17.3%)	68	15/99 (15.2%)	15	9/47 (19.1%)	9
Insomnia	26/664 (3.9%)	26	6/56 (10.7%)	6	1/15 (6.7%)	1	10/394 (2.5%)	10	8/99 (8.1%)	8	3/47 (6.4%)	3
Tremor	0/664 (0%)	0	0/56 (0%)	0	1/15 (6.7%)	1	0/394 (0%)	0	0/99 (0%)	0	0/47 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/664 (1.4%)	9	8/56 (14.3%)	8	0/15 (0%)	0	11/394 (2.8%)	11	9/99 (9.1%)	9	1/47 (2.1%)	1
Bronchitis	5/664 (0.8%)	5	3/56 (5.4%)	3	0/15 (0%)	0	2/394 (0.5%)	2	2/99 (2%)	2	0/47 (0%)	0
Cough	15/664 (2.3%)	15	3/56 (5.4%)	3	0/15 (0%)	0	14/394 (3.6%)	14	3/99 (3%)	3	0/47 (0%)	0
Nasal Congestion	2/664 (0.3%)	2	0/56 (0%)	0	1/15 (6.7%)	1	3/394 (0.8%)	3	0/99 (0%)	0	0/47 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	10/664 (1.5%)	10	3/56 (5.4%)	3	0/15 (0%)	0	2/394 (0.5%)	2	4/99 (4%)	4	4/47 (8.5%)	4
Rash	10/664 (1.5%)	10	2/56 (3.6%)	2	1/15 (6.7%)	1	5/394 (1.3%)	5	3/99 (3%)	3	3/47 (6.4%)	3
Vascular disorders
Oedema Peripheral	12/664 (1.8%)	12	1/56 (1.8%)	1	1/15 (6.7%)	1	4/394 (1%)	4	1/99 (1%)	1	0/47 (0%)	0

Limitations/Caveats

This pragmatic trial allowed patients who were randomized to SOF/LDV but unable to obtain SOF/LDV (due to limitations in access from insurance, etc.) to be treated with the accessible, alternative DAA regimens. This contributed to the variance from 'as randomized' population to the 'as treated' population. Rapidly changing HCV landscape led to discontinuation of PrOD treatment regimen and modification of initial analysis plan including reduction of original sample size.

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Lauren Morelli
Organization	UF Hepatology Research at CTRB
Phone	352-273-9508
Email	lauren.morelli@medicine.ufl.edu

Responsible Party:

University of Florida

ClinicalTrials.gov Identifier:

NCT02786537

Other Study ID Numbers:

16-1234
PCORI-1503-27891
IRB201501162

First Posted:

Jun 1, 2016

Last Update Posted:

Dec 6, 2021

Last Verified:

Dec 1, 2021

PRIORITIZE: Study of Oral Treatments for Hepatitis C

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact