A Comparison of the Effectiveness, Safety, and Tolerability of Two Different Hepatitis C Treatments in Patients Infected With Both HIV and Hepatitis C Virus (HCV)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT00008463
Collaborator
(none)
132
24
69
5.5
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to see if treatment with PEG-interferon-alfa-2a (PEG-IFN) plus ribavirin is a more effective treatment for hepatitis C virus (HCV) than interferon-alfa-2a (IFN) plus ribavirin for patients infected with both HCV and HIV. The study will also compare the 2 regimens to see which has fewer side effects.

HCV infection is common in patients infected with HIV. Patients infected with both HIV and HCV viruses seem to have more severe hepatitis C. A combination of IFN and ribavirin has been shown to lessen the severity of HCV. PEG-IFN is a modified form of IFN that stays in the blood longer, which means that patients would not have to take the treatment as often. This study will compare the safety and effectiveness of PEG-IFN to IFN when each is combined with ribavirin.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Infection with HCV is common in patients infected with HIV owing to similar routes of transmission. The cellular immunosuppression caused by HIV infection appears to lead to an increased HCV plasma load, more progressive liver disease, and, in patients with chronic hepatitis C, increased mortality. Ribavirin treatment combined with IFN has shown improved sustained virologic response rates over IFN monotherapy. PEG-IFN, a chemically modified formulation of IFN, circulates for a much longer time in the blood than the parent compound. Pharmacokinetic and pharmacodynamic data suggest that PEG-IFN injected weekly would have the potential for superior efficacy as compared with IFN injected 3 times per week. The efficacy and safety profiles of combination therapy with PEG-IFN and ribavirin are not well known. This study will compare combination therapy consisting of PEG-IFN and ribavirin with that of IFN and ribavirin.

Patients are stratified according to HCV genotype and CD4 count and viral load, then randomized to either Arm A (IFN plus ribavirin) or Arm B (PEG-IFN plus ribavirin). Patients receive up to 48 weeks of treatment. Virologic response is assessed at Week 24 and a decision to continue or discontinue treatment is made. If a virologic response is shown at Week 24, the patient continues treatment for an additional 24 weeks. If no virologic response is observed, then the histologic response is assessed by a liver biopsy. If biopsy shows a histologic response is present, treatment is continued for 24 weeks. If biopsy shows no histologic response, treatment is discontinued. [AS PER AMENDMENT 07/20/01: Patients with virologic response who discontinue after Week 24 will have liver biopsy at time of discontinuation. Patients with no virologic response continuing study treatment after having a liver biopsy within 2 weeks of Week 24, who also demonstrate histologic response and decide to discontinue after Week 24, are strongly encouraged to have a 2nd liver biopsy at the end of treatment. Patients with no virologic response who discontinue after Week 24 will not have liver biopsy at time of discontinuation.] Physical examinations are done regularly and blood samples collected for routine laboratory tests, confidential genetic testing, and to measure HCV and HIV-1 plasma viral loads. Women able to become pregnant have regular pregnancy tests. All patients are followed for an additional 24 weeks after treatment discontinuation.

Patients may enroll in 1 or none of the following substudies: A5091s, Hepatic C Viral Kinetics in Subjects Co-infected with Human Immunodeficiency Virus-1 (HIV-1) and Hepatitis C Virus Genotype 1 (HCV-1); [AS PER AMENDMENT 07/20/01: The following text has been deleted: or A5092s, Evaluation of the Effects of Ribavirin on Zidovudine (ZDV) or Stavudine (d4T) Triphosphate Formation] [AS PER AMENDMENT 07/20/01: Substudy A5092s, Evaluation of the Effects of Ribavirin on Zidovudine (ZDV) or Stavudine (d4T) Triphosphate Formation is now a stand-alone study.]

Study Design

Study Type:
Interventional
Primary Purpose:
Treatment
Official Title:
A Prospective, Multicenter, Phase II/III, Open-Label, Controlled, Randomized Trial Evaluating the Efficacy, Safety, and Tolerability of Interferon-alfa-2a Plus Ribavirin Versus PEG-interferon-alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus (HCV) Infection in Individuals Co-Infected With Human Immunodeficiency Virus-1 (HIV-1)
Study Start Date :
Nov 1, 2000
Study Completion Date :
Aug 1, 2006

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    Patients may be eligible for this study if they:
    • Are HIV-positive.

    • Have chronic liver disease consistent with chronic hepatitis C.

    • Have evidence of hepatitis C within the 48 weeks prior to entry.

    • Are 18 to 65 years old.

    • Agree to use 2 barrier methods of birth control during the study and for 6 months after stopping the medications.

    • Meet 1 of the following sets of guidelines: 1) have a CD4 count of more than 100 cells/mm3 and have a viral load (level of HIV in the blood) of less than 10,000 copies/ml within 35 days prior to study entry, and have taken stable anti-HIV drugs for at least 12 weeks prior to study entry and plan to remain on the same treatment for the first 24 weeks of the study; or 2) have a CD4 count of more than 300 cells/mm3 within 35 days prior to study entry and have not taken any anti-HIV drugs in the 12 weeks prior to entry, and do not plan to start anti-HIV treatment within the first 24 weeks of study entry.

    Exclusion Criteria

    Patients will not be eligible for this study if they:
    • Have a positive test for hepatitis B.

    • Show evidence of medical conditions associated with long-term liver disease other than HCV.

    • Have severe mental illness, especially depression, or have been hospitalized for mental illness within the previous 24 weeks.

    • Are allergic to any of the study products.

    • Have uncontrolled seizures.

    • Have had or currently have any immune diseases.

    • Have lung disease such that function is limited.

    • Have had evidence of heart disease or certain heart problems within 24 weeks of study entry.

    • Have severe retinopathy (eye disease).

    • Have had a major organ transplant and still have the graft.

    • Have any other severe disease or cancer that would interfere with the study.

    • Have had anti-cancer or immune-regulating drugs or radiation treatment within 24 weeks of study entry or expect to need such treatment during the study.

    • Have received rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, hydroxyurea, granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 6 weeks of study entry.

    • Abuse drugs or alcohol. Patients in methadone programs may participate.

    • Have a blood disorder such as thalassemia.

    • Have received interferon or oral ribavirin therapy.

    • Have taken an experimental drug that affects HCV, within 6 weeks of study entry.

    • Need to use during the study any of the drugs prohibited by the study.

    • Have had an opportunistic (AIDS-related) infection within 4 weeks of study entry.

    • Are pregnant or breast-feeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ucsd, Avrc Crs San Diego California United States 92103
    2 Ucsf Aids Crs San Francisco California United States 941104206
    3 University of Colorado Hospital CRS Aurora Colorado United States 80262
    4 Univ. of Miami AIDS CRS Miami Florida United States 331361013
    5 The Ponce de Leon Ctr. CRS Atlanta Georgia United States 30308
    6 Univ. of Hawaii at Manoa, Leahi Hosp. Honolulu Hawaii United States 96816
    7 Indiana Univ. School of Medicine, Infectious Disease Research Clinic Indianapolis Indiana United States 462025250
    8 Indiana Univ. School of Medicine, Wishard Memorial Indianapolis Indiana United States 46202
    9 Methodist Hosp. of Indiana Indianapolis Indiana United States 46202
    10 Univ. of Iowa Healthcare, Div. of Infectious Diseases Iowa City Iowa United States 52242
    11 Massachusetts General Hospital ACTG CRS Boston Massachusetts United States 02114
    12 Bmc Actg Crs Boston Massachusetts United States 02118
    13 Beth Israel Deaconess Med. Ctr., ACTG CRS Boston Massachusetts United States 02215
    14 Brigham and Women's Hosp. ACTG CRS Boston Massachusetts United States 02215
    15 University of Minnesota, ACTU Minneapolis Minnesota United States 55455
    16 Beth Israel Med. Ctr., ACTU New York New York United States 10003
    17 NY Univ. HIV/AIDS CRS New York New York United States 10016
    18 Mt. Sinai Med. Ctr. A0404 CRS New York New York United States 10029
    19 HIV Prevention & Treatment CRS New York New York United States
    20 AIDS Care CRS Rochester New York United States 14642
    21 Univ. of Rochester ACTG CRS Rochester New York United States 14642
    22 Univ. of Cincinnati CRS Cincinnati Ohio United States 452670405
    23 Philadelphia Veterans Admin. Med. Ctr. A6205 CRS Philadelphia Pennsylvania United States 19104
    24 Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic Dallas Texas United States 75390

    Sponsors and Collaborators

    • National Institute of Allergy and Infectious Diseases (NIAID)

    Investigators

    • Study Chair: Raymond Chung, MD, Harvard/Massachusetts General Hospital
    • Study Chair: Paul Volberding, MD, San Francisco General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT00008463
    Other Study ID Numbers:
    • A5071
    • 10675
    • Substudy AACTG A5091s
    • ACTG A5071
    • AACTG A5071
    First Posted:
    Aug 31, 2001
    Last Update Posted:
    Nov 1, 2021
    Last Verified:
    Oct 1, 2021

    Study Results

    No Results Posted as of Nov 1, 2021