Clinical trial NCT02858180: Hepatitis C Virus(HCV) Heart and Lung Study
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C, Chronic
Heart Failure
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Interstitial
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2016-08-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects Who Completed 24 Weeks of Therapy
timeFrame: 24 weeks
Secondary outcomes:
measure: Number of Subjects With Sustained Virologic Response (SVR) 12
timeFrame: 12 weeks after completing treatment
measure: Number of Subjects With Sustained Virologic Response (SVR) 4
timeFrame: 4 weeks after completing treatment
Other outcomes:
measure: Discontinuation for Adverse Events and Serious Adverse Events
timeFrame: 12 weeks after completing treatment
Locations:
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center - Dept of Gastroenterology
state: North Carolina
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: Duke University
name: Andrew Muir, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.7326/0003-4819-144-10-200605160-00004.
citation: 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. No abstract available.
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citation: 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.
citation: 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.
citation: 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. doi: 10.1016/s1053-2498(01)00255-8.
citation: 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. doi: 10.1016/j.healun.2007.01.037. Epub 2007 Mar 26.
citation: 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.