Smartphone Based aDOT Treatment With Fixed-Dose Elbasvir and Grazoprevir in PWIDs

• Sponsor: Albert Einstein College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT03127358
• Collaborator: AiCure (Industry), Merck Sharp & Dohme LLC (Industry)
• Enrollment: 11
• Location: 1
• Arms: 3
• Actual Duration (Months): 14.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

People who Inject Drugs (PWIDs) constitute 60% of the approximately 5 million people in the United States infected with hepatitis C virus (HCV). Successful HCV treatment leading to sustained viral response (SVR) is associated with increased survival, but to date successful treatment of PWIDs has been limited. Treatment of PWIDs is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. At Albert Einstein College of Medicine, the investigators have developed a multidisciplinary model of HCV care that integrates on-site primary care, substance abuse treatment, and HCV-related care within opiate agonist treatment clinics. To optimize HCV treatment outcomes, the investigators have introduced directly observed therapy (DOT). In the DOT model, one daily dose of oral HCV medication is administered with methadone. However, DOT is not feasible for PWIDs who are not enrolled in methadone maintenance treatment programs, and is less effective for methadone-maintained PWIDs who do not attend the methadone clinics every day. In addition, DOT has been used for decades both to measure and maximize adherence for treatment of tuberculosis infection, but the cost and logistical complexity of administering DOT for large HCV clinical programs would be prohibitive.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C; Medication Adherence	Device: AiCure; Device: AiCure with gamification	N/A

Detailed Description

Automated DOT (a-DOT), a smartphone app that uses facial recognition software and advanced features to detect non-ingestion, combines the accuracy of in-person DOT with the convenience of real-time centralized data collection and monitoring. Adding a daily side effect diary to a-DOT will further allow precise tracking of timing of both medication ingestion and side effects which may be compromising adherence. Zepatier (elbasvir and grazoprevir) is a new once-daily fixe-dose combination tablet which has achieved high rates of SVR ranging from 94 to 97 percent in genotype-1 infected patients including those with HIV/HCV coinfection and renal impairment. Zepatier is administered for 12 to 16 weeks, depending on HCV genotype, prior treatment history, and the presence of certain baseline NS5A polymorphisms (1a only). By administering Zepatier via this innovative a-DOT platform, the investigators hypothesize that PWIDs treated in real-wrold settings can be successfully treated with high rates of adherence and SVR.

In this proposed 18-month trials, 75 PWIDs enrolled in opiate agonist treatment (genotypes 1a and 1b) with chronic HCV will be enrolled over a 12-month period, and randomized to either aDOT or treatment as usual (TAU). The investigators will recruit PWIDs from diverse community settings include a syringe exchange program (NYHRE), federally-qualified health center (Comprehensive Health Care Center), homeless shelter (The Living Room), and a methadone maintenance treatment program (Montefiore Wellness Centers). All patients (inlcuding treatment-experienced and HIVV/HCV coinfected subjects) will be treated with Zepatier-based regimens as per the standard of care. Rigorous data are necessary to judge the contribution of a-DOT to the success of HCV treatment in PWIDs. By performing a randomized trial of a-DOT HCV therapy (Zepatier with and without ribavirin), the investigators will evaluate the efficacy of a-DOT for improving HCV treatment outcomes among PWIDs.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Smartphone Based Automated-Directly Observed Treatment Improves Adherence and SVR to Fixed-Dose Elbasvir and Grazoprevir in PWIDs: A Randomized Control Trial
• Actual Study Start Date: Nov 14, 2017
• Actual Primary Completion Date: Feb 6, 2019
• Actual Study Completion Date: Feb 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AiCure App Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks.	Device: AiCure; Smartphone App; Other Names: a-DOT, Smartphone App
No Intervention: Treatment As Usual Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app.
Active Comparator: AiCure with gamification Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication.	Device: AiCure with gamification; Smartphone App with gaming.; Other Names: a-DOT with gamification

Outcome Measures

Primary Outcome Measures

1. HCV Treatment Adherence [12 weeks]

   The amount of medication taken by each patient during the treatment period is expressed as a percentage (range 0-100%). Subjects will be classified as "adherent" if they receive at least 80% of the total dose of Zepatier. The numbers below denotes the mean percent of the medication the participants in each arm took.

Secondary Outcome Measures

1. Number of Participants With HCV Treatment Completion [12 weeks]

   Participants will be considered to have completed treatment if they have completed at least 80% of the planned treatment course (e.g. at least 10 week of 12-week course).

2. Number of Participants With Sustained Viral Response (SVR) [12 weeks post treatment]

   HCV viral load undectable 12 weeks after treatment completion. Undetectable HCV viral load is defined as <15 IU/ml and "target not detected". IU refers to "international units".One of the main outcomes looked for was the amount of patients who achieved Sustained Virologic Response (SVR) at 12 weeks post treatment, which denotes a cure of Hepatitis C.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HCV-infected (HCV RNA test above the limit of quantification at baseline)

• Genotypes/Subtypes: G1a or G1b

• Eligible for HCV treatment per 2016 AASLD/IDSA guidelines

• Willing to receive HCV treatment on-site at DoSA clinics

• Health care provider decision to treat patient with Zepatier-based therapy with or without ribavirin based on 2016 AASLD/IDSA guidelines

• Using illicit drugs (either opiates, cocaine, or benzodizepenes) within the last 6 months

• Age 18 or older

• Able to provide informed consent

• English or Spanish speaking

Exclusion Criteria:

• Known hypersensitivity (allergy) to elbasvir, grazoprevir, or ribavirin

• Pregnant or breast-feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein College of Medicine Division of Substance Abuse clinics	Bronx	New York	United States	10461

Sponsors and Collaborators

• Albert Einstein College of Medicine
• AiCure
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Julia Arnsten, MD, Montefiore Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2018
• Informed Consent Form - Mar 23, 2018

More Information

Publications

None provided.

• Responsible Party: Julia H. Arnsten, Professor, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT03127358
• Other Study ID Numbers: 2016-7215
• First Posted: Apr 25, 2017
• Last Update Posted: Sep 14, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Julia H. Arnsten, Professor, Albert Einstein College of Medicine: Addiction; Sustained Viral Response; Adherence; Adverse Effects; Direct Acting Antiviral Agent; Chronic Hepatitis C; Resistance Development; Methadone Clinic; Primary Care; Directly Observed Therapy; Randomized Controlled Trial; Resistance; Reinfection; Treatment Outcome; Patient Navigation; Multi-Site; Liver Disease; Intervention
• Additional relevant MeSH terms: Hepatitis C; Hepatitis

Study Results

Participant Flow

Recruitment Details	Recruitment dates were from 11/14/17 to 7/20/18, during which 11 participants were recruited and enrolled into the study. Participants were recruited from a Montefiore Medical Center opioid treatment program in the Bronx. Participants were identified through chart review and provider referral, and through participant self-referral.

Arm/Group Title	AiCure App	Treatment As Usual	AiCure With Gamification
Arm/Group Description	Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. AiCure: Smartphone App	Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app.	Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. AiCure with gamification: Smartphone App with gaming.
Period Title: Overall Study
STARTED	3	3	5
COMPLETED	3	3	5
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	AiCure App	Treatment As Usual	AiCure With Gamification	Total
Arm/Group Description	Direct Observed Therapy via the AiCure app (a-DOT)	Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app.	Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. AiCure with gamification: Smartphone App with gaming.	Total of all reporting groups
Overall Participants	3	3	5	11
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53	60	58	57
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	2 40%	3 27.3%
Male	2 66.7%	3 100%	3 60%	8 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	1 33.3%	4 80%	6 54.5%
Not Hispanic or Latino	2 66.7%	2 66.7%	1 20%	5 45.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 66.7%	1 33.3%	1 20%	4 36.4%
White	0 0%	2 66.7%	4 80%	6 54.5%
More than one race	1 33.3%	0 0%	0 0%	1 9.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	5 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	HCV Treatment Adherence
Description	The amount of medication taken by each patient during the treatment period is expressed as a percentage (range 0-100%). Subjects will be classified as "adherent" if they receive at least 80% of the total dose of Zepatier. The numbers below denotes the mean percent of the medication the participants in each arm took.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AiCure App	Treatment As Usual	AiCure With Gamification
Arm/Group Description	Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. AiCure: Smartphone App	Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app.	Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. AiCure with gamification: Smartphone App with gaming.
Measure Participants	3	3	5
Mean (Full Range) [percent of medication taken]	83	100	88

2. Secondary Outcome

Title	Number of Participants With HCV Treatment Completion
Description	Participants will be considered to have completed treatment if they have completed at least 80% of the planned treatment course (e.g. at least 10 week of 12-week course).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AiCure App	Treatment As Usual	AiCure With Gamification
Arm/Group Description	Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. AiCure: Smartphone App 3 out 3 patients completed HCV treatment.	Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app. 3 out 3 patients completed HCV treatment.	Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. AiCure with gamification: Smartphone App with gaming. 5 out 5 patients completed HCV treatment.
Measure Participants	3	3	5
Count of Participants [Participants]	3 100%	3 100%	5 100%

3. Secondary Outcome

Title	Number of Participants With Sustained Viral Response (SVR)
Description	HCV viral load undectable 12 weeks after treatment completion. Undetectable HCV viral load is defined as <15 IU/ml and "target not detected". IU refers to "international units".One of the main outcomes looked for was the amount of patients who achieved Sustained Virologic Response (SVR) at 12 weeks post treatment, which denotes a cure of Hepatitis C.
Time Frame	12 weeks post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AiCure App	Treatment As Usual	AiCure With Gamification
Arm/Group Description	Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. AiCure: Smartphone App 3 out 3 patients achieved SVR.	Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app. 3 out 3 patients achieved SVR.	Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. AiCure with gamification: Smartphone App with gaming. 5 out 5 patients achieved SVR.
Measure Participants	3	3	5
Number [percent of patients with SVR]	100	100	100

Adverse Events

Time Frame	The study participants were assessed from 4 months prior to enrollment, through 12 weeks of treatment, to 7 months after treatment, an average of 14 months
Adverse Event Reporting Description	The definition of adverse event and/or serious adverse event does not differ from the definitions on clinicaltrials.gov.
Arm/Group Title	AiCure App		Treatment As Usual		AiCure With Gamification
Arm/Group Description	Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. AiCure: Smartphone App		Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app.		Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. AiCure with gamification: Smartphone App with gaming.
All Cause Mortality
	AiCure App		Treatment As Usual		AiCure With Gamification
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/5 (0%)
Serious Adverse Events
	AiCure App		Treatment As Usual		AiCure With Gamification
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	AiCure App		Treatment As Usual		AiCure With Gamification
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/5 (0%)

Limitations/Caveats

Early termination due to discontinued funding led to small numbers of subjects analyzed, and study personnel were no longer available to work on this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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.