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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00008463
First received: January 9, 2001
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
HIV Infections
Hepatitis C
Drug: Ribavirin
Drug: Interferon alfa-2a
Drug: Peginterferon alfa-2a
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 132
Study Start Date: November 2000
Estimated Study Completion Date: August 2006
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.]

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008463

Locations
United States, California
Ucsd, Avrc Crs
San Diego, California, United States, 92103
Ucsf Aids Crs
San Francisco, California, United States, 941104206
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Georgia
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States, 30308
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 462025250
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States, 46202
United States, Iowa
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
Mt. Sinai Med. Ctr. A0404 CRS
New York, New York, United States, 10029
HIV Prevention & Treatment CRS
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
AIDS Care CRS
Rochester, New York, United States, 14642
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Philadelphia Veterans Admin. Med. Ctr. A6205 CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Investigators
Study Chair: Raymond Chung, MD Harvard Massachusetts General Hospital
Study Chair: Paul Volberding, MD San Francisco General Hospital
  More Information

Additional Information:
Publications:
R Chung, J Andersen, P Volberding, G Robbins, T Liu, K Sherman, M Peters, M Koziel, B Alston, D Colquhoun, T Nevin, G Harb, C van der Horst, and AIDS Clinical Trials Group A5071 Study Team: A Randomized, Controlled Trial of PEG-Interferon-alfa-2a plus Ribavirin vs Interferon-alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV-co-infected Persons: Follow-up Results of ACTG A5071. CROI 2004. Abstract 110.

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00008463     History of Changes
Other Study ID Numbers: A5071, 10675, Substudy AACTG A5091s, ACTG A5071, AACTG A5071
Study First Received: January 9, 2001
Last Updated: June 7, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Ribavirin
Polyethylene Glycols
Interferon Alfa-2a
HIV-1
Antiviral Agents
Hepatitis C, Chronic

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis A
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Interferon-alpha
Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014