Hepatitis C Virus(HCV) Heart and Lung Study

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02858180
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 15
• Locations: 4
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter study in Hepatitis C Virus (HCV) infected adult patients who also have advanced cardiac disease or advanced lung disease.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic; Heart Failure; Pulmonary Disease, Chronic Obstructive; Lung Diseases, Interstitial	Drug: Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC)	Phase 4

Detailed Description

This is a multicenter study in HCV infected adult patients who also have either advanced cardiac disease, or advanced lung disease. Advanced cardiac disease is defined as a marked limitation of physical activity, or discomfort upon physical activity. The patients in the advanced cardiac disease group must also have been hospitalized for heart failure within the last 12 months.

Advanced lung disease is defined as patients who have been diagnosed with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). Patients in the COPD group must have abnormalities in their forced expiratory volume (FEV) test, which measures the amount of air exhaled. They may or may not need supplemental oxygen. Patients in the ILD group must have been diagnosed with ILD and require supplement oxygen at all times.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label Study of Harvoni ® (Sofosbuvir Ledipasvir Fixed Dose Combination) in Subjects Infected With Chronic Hepatitis C and Advanced Heart Failure or Lung Disease
• Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Apr 11, 2019
• Actual Study Completion Date: Jul 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Heart Failure Cohort Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV)	Drug: Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC); 1 pill once daily of SOF/LDV FDC; Other Names: Harvoni
Experimental: Lung Disease Cohort Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir	Drug: Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC); 1 pill once daily of SOF/LDV FDC; Other Names: Harvoni

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Completed 24 Weeks of Therapy [24 weeks]

   The primary safety endpoint is the number of subjects who complete a full course of therapy.

Secondary Outcome Measures

1. Number of Subjects With Sustained Virologic Response (SVR) 12 [12 weeks after completing treatment]

   The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 12 weeks after completing therapy.

2. Number of Subjects With Sustained Virologic Response (SVR) 4 [4 weeks after completing treatment]

   The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 4 weeks after completing treatment.

Other Outcome Measures

1. Discontinuation for Adverse Events and Serious Adverse Events [12 weeks after completing treatment]

   Assessment for discontinuation due to adverse events and serious adverse events, as addressed by adverse events and laboratory tests. Final study visit is 12 weeks after treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Chronic HCV Infection of Genotype 1, 4, 5, or 6

• HCV RNA > 103 IU/mL at screening

• 18 years of age or older

• Diagnosis of chronic HCV infection, defined as positive HCV antibody or HCV RNA more than 6 months prior to screening OR an assessment of fibrosis F2 or greater prior to screening.

Subjects in the advanced heart failure cohort must meet all HCV criteria, and all of the following criteria:

• New York Heart Association (NYHA) Class III or IV functional classification

• NYHA Class III: Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.

• NYHA Class IV: Patient with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

• ejection fraction ≤ 30%

• hospitalized for heart failure in last 12 months

Subjects in the advanced lung disease cohort must have been diagnosed with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) must meet all HCV criteria, and meet the following criteria for COPD or ILD:

• ILD criteria: diagnosis of interstitial lung disease with chronic supplemental oxygen requirement at rest and/or with exertion.

• COPD criteria (one of the following):

• Forced expiratory volume (FEV1)< 30% predicted

• OR any FEV1 with chronic supplemental oxygen requirement at rest and/or with exertion

• OR any FEV1 with chronic hypercapnia (baseline partial pressure of arterial carbon dioxide [PaCO2] > 45)

Exclusion Criteria:

• Chronic HCV Infection with Genotype 2 or 3

• Treatment with any of the following agents

• Amiodarone. Subjects previously treated with amiodarone must have stopped the amiodarone at least 60 days prior to day 1 of SOF/LDV FDC

• Carbamazepine, phenytoin, phenobarbital, oxcarbazepine

• Rifabutin, rifampin or rifapentine

• HIV regimens containing tenofovir or tipranavir/ritonavir

• St. John's wort

• Rosuvastatin

• Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance

• History of hepatic encephalopathy or variceal hemorrhage

• Hepatitis B surface antigen positive

• Abnormal hematological and biochemical parameters, including:

• Hemoglobin (Hb) < 8 g/dL

• Platelets ≤ 50,000/mm3

• alanine aminotransferase (ALT), aspartase aminotransferase (AST), or alkaline phosphatase ≥ 10 times upper limit of normal(ULN)

• Total bilirubin > 3 mg/dl

• Severe renal impairment creatinine clearance (CrCl), i.e. < 30 mL/min.

• History of major organ transplantation with an existing functional graft.

• History of clinically-significant drug allergy to nucleoside/nucleotide analogs.

• Pregnant women or women planning to become pregnant

• Women who are breastfeeding

• Active or recent history (≤ 1 year) of drug or alcohol abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Henry Ford Health System	Detroit	Michigan	United States	48377
2	Columbia University Medical Center	New York	New York	United States	10032
3	Duke University Medical Center - Dept of Gastroenterology	Durham	North Carolina	United States	27705
4	Harborview Medical Center	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Duke University
• Gilead Sciences

Investigators

• Principal Investigator: Andrew Muir, MD, Duke University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 12, 2016

More Information

Publications

• Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.
• Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.
• Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14.
• Fagiuoli S, Minniti F, Pevere S, Farinati F, Burra P, Livi U, Naccarato R, Chiaramonte M. HBV and HCV infections in heart transplant recipients. J Heart Lung Transplant. 2001 Jul;20(7):718-24.
• Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, Crawford D, Weiland O, Aguilar H, Xiong J, Pilot-Matias T, DaSilva-Tillmann B, Larsen L, Podsadecki T, Bernstein B. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014 Apr 24;370(17):1594-603. doi: 10.1056/NEJMoa1315722. Epub 2014 Apr 10.
• Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74. doi: 10.1002/hep.22759.
• Lee I, Localio R, Brensinger CM, Blumberg EA, Lautenbach E, Gasink L, Amorosa VK, Lo Re V 3rd. Decreased post-transplant survival among heart transplant recipients with pre-transplant hepatitis C virus positivity. J Heart Lung Transplant. 2011 Nov;30(11):1266-74. doi: 10.1016/j.healun.2011.06.003. Epub 2011 Jul 20.
• Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013 Apr;57(4):1333-42. doi: 10.1002/hep.26141. Epub 2013 Feb 4. Review.
• Sahi H, Zein NN, Mehta AC, Blazey HC, Meyer KH, Budev M. Outcomes after lung transplantation in patients with chronic hepatitis C virus infection. J Heart Lung Transplant. 2007 May;26(5):466-71. Epub 2007 Mar 26.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02858180
• Other Study ID Numbers: Pro00069602
• First Posted: Aug 8, 2016
• Last Update Posted: Apr 21, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Lung Diseases, Interstitial; Heart Failure; Sofosbuvir; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Between 12/2016 and 12/2018, 15 subjects with chronic HCV and advanced heart failure or chronic HCV and lung disease were enrolled across 4 sites (academic medical centers in the US). Subjects all have genotype 1, 4, 5 or 6 HCV.

Arm/Group Title	Heart Failure Cohort	Lung Disease Cohort
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC
Period Title: Overall Study
STARTED	10	5
COMPLETED	10	3
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Heart Failure Cohort	Lung Disease Cohort	Total
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Total of all reporting groups
Overall Participants	10	5	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (7.5)	59.4 (5.1)	60.1 (6.6)
Sex: Female, Male (Count of Participants)
Female	3 30%	3 60%	6 40%
Male	7 70%	2 40%	9 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	10 100%	5 100%	15 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 70%	3 60%	10 66.7%
White	3 30%	2 40%	5 33.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	5 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Completed 24 Weeks of Therapy
Description	The primary safety endpoint is the number of subjects who complete a full course of therapy.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heart Failure Cohort	Lung Disease Cohort
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC
Measure Participants	10	5
Count of Participants [Participants]	0 0%	1 20%

2. Secondary Outcome

Title	Number of Subjects With Sustained Virologic Response (SVR) 12
Description	The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 12 weeks after completing therapy.
Time Frame	12 weeks after completing treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heart Failure Cohort	Lung Disease Cohort
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC
Measure Participants	10	5
Count of Participants [Participants]	10 100%	3 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Heart Failure Cohort, Lung Disease Cohort
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	86.7
	Confidence Interval	(2-Sided) 95%; 59.5 to 98.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Subjects With Sustained Virologic Response (SVR) 4
Description	The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 4 weeks after completing treatment.
Time Frame	4 weeks after completing treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heart Failure Cohort	Lung Disease Cohort
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC
Measure Participants	10	5
Count of Participants [Participants]	8 80%	3 60%

4. Other Pre-specified Outcome

Title	Discontinuation for Adverse Events and Serious Adverse Events
Description	Assessment for discontinuation due to adverse events and serious adverse events, as addressed by adverse events and laboratory tests. Final study visit is 12 weeks after treatment.
Time Frame	12 weeks after completing treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heart Failure Cohort	Lung Disease Cohort
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC
Measure Participants	10	5
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Up to 36 weeks
Arm/Group Title	Heart Failure Cohort		Lung Disease Cohort
Arm/Group Description	Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC		Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC): 1 pill once daily of SOF/LDV FDC
All Cause Mortality
	Heart Failure Cohort		Lung Disease Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/5 (0%)
Serious Adverse Events
	Heart Failure Cohort		Lung Disease Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Heart Failure Cohort		Lung Disease Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.