Efficacy of Pegylated Interferon on Liver Fibrosis in Co-infected Patient With HIV and Hepatitis C - Full Text View

Purpose

The aim of this study is to prove the efficacy of peginterferon in HIV infected patients with liver disease caused by hepatitis C virus (HCV) when the treatment to eradicate the virus failed. This scientific proof needs a comparative study to be done including two groups of patients randomly allocated: one with the treatment (peginterferon) and the other without any treatment against HCV with a duration of 2 years. To conclude, two liver biopsies are needed; one before the study and a second 2 years after.

Condition	Intervention	Phase
HIV Infections Hepatitis C, Chronic	Biological: Peginterferon alpha-2a (Pegasys®) Drug: Ribavirin Drug: HIV antiretroviral therapy	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Efficacy of Pegylated Interferon on Liver Fibrosis in Co-infected Patient With HIV and C Hepatitis Who Failed to Active Treatment for HCV. ANRSHC12 Fibrostop

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Ribavirin Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:

Percentage of patients who experienced one point decreases of their fibrosis histological score (Metavir). [ Time Frame: Week 96 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Distribution of the change of fibrosis Metavir score in each group [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Distribution of fibrosis score from Chevallier classification [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Plasmatic fibrosis markers dosages [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Viral load quantification for HIV and HCV [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Number and percentage of CD4/CD8 cell count throughout the study [ Time Frame: Day 0 to week 96 ] [ Designated as safety issue: No ]
Number and percentage of patient had more thand 200 copies/ml throughout the study [ Time Frame: Day 0 to week 96 ] [ Designated as safety issue: No ]
Occurrence of hepatic complication related to HCV [ Time Frame: Day0 to week 96 ] [ Designated as safety issue: No ]
Survival throughout the study [ Time Frame: Day 0 to week 96 ] [ Designated as safety issue: No ]
Quality of life questionnaire [ Time Frame: Day 0 to week 96 ] [ Designated as safety issue: No ]
Fibrotest (plasmatic fibrosis marker) [ Time Frame: Day 0, week 48 and week 96 ] [ Designated as safety issue: No ]
Histological improvement according to the total interferon dose received [ Time Frame: Day 0 to week 96 ] [ Designated as safety issue: No ]


Enrollment:	52
Study Start Date:	November 2003
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Peginterféron alpha-2a + Ribavirin+ HIV antiretroviral therapy Day0 to week 96:Peginterféron alpha-2a + Ribavirin+ HIV antiretroviral therapy	Biological: Peginterferon alpha-2a (Pegasys®) Peg-Interferon Alpha2a by subcutaneous injection, 180µg, once weekly Drug: Ribavirin Ribavirin: tablet oral, weight-based dose, 1000 mg for subjects weighing below 75 kg or 1200 mg for subjects weighing equal or over 75 kg, once daily Drug: HIV antiretroviral therapy All antiretroviral drugs are allowed, their choice being left to the discretion of the investigator. Particular attention will be carried to the patients with antiretroviral susceptible to cause a cumulative toxicity with anti-VHC drugs
Placebo Comparator: HIV antiretroviral therapy Day0 to week 96: HIV antiretroviral therapy	Drug: HIV antiretroviral therapy All antiretroviral drugs are allowed, their choice being left to the discretion of the investigator. Particular attention will be carried to the patients with antiretroviral susceptible to cause a cumulative toxicity with anti-VHC drugs

Arms

Assigned Interventions

Active Comparator: Peginterféron alpha-2a + Ribavirin+ HIV antiretroviral therapy

Day0 to week 96:Peginterféron alpha-2a + Ribavirin+ HIV antiretroviral therapy

Biological: Peginterferon alpha-2a (Pegasys®)

Peg-Interferon Alpha2a by subcutaneous injection, 180µg, once weekly

Drug: Ribavirin

Ribavirin: tablet oral, weight-based dose, 1000 mg for subjects weighing below 75 kg or 1200 mg for subjects weighing equal or over 75 kg, once daily

Drug: HIV antiretroviral therapy

All antiretroviral drugs are allowed, their choice being left to the discretion of the investigator. Particular attention will be carried to the patients with antiretroviral susceptible to cause a cumulative toxicity with anti-VHC drugs

Placebo Comparator: HIV antiretroviral therapy

Day0 to week 96: HIV antiretroviral therapy

Drug: HIV antiretroviral therapy

All antiretroviral drugs are allowed, their choice being left to the discretion of the investigator. Particular attention will be carried to the patients with antiretroviral susceptible to cause a cumulative toxicity with anti-VHC drugs

Detailed Description:

C hepatitis in HIV infected patient becomes a major issue although the survival of patients, has improved in the last decades regarding to the advent of HAART, the mortality related to liver disease has increased in this population. Sustained virological response for HCV can be obtained with peg-interferon and ribavirin treatment but more or less 50% of patients experienced failure to this treatment and liver fibrosis due to HCV infection progress and may lead to cirrhosis and hepato-carcinoma. To demonstrate the efficacy of peginterferon therapy to reduce the liver damage causes by HCV infection, a randomised controlled study is needed comparing one group of patient treated by peginterferon and one group without any treatment against HCV infection. In order to show 30% difference between the two groups in reducing one point of fibrosis score (METAVIR scale), 150 patients are needed. The duration of the study is 96 weeks

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infection (Western Blot +)
C hepatitis (RNA viral hepatitis C [VHC] +)
Chronic active C hepatitis on liver histological score METAVIR (A over or equal to 1 and F over or equal to 2) on biopsy performed at least 18 months before the expected date of inclusion
Previous treatment for C hepatitis for at least 3 months including peg-interferon and ribavirin or peg-interferon alone if counterindication for ribavirin occurred
Failure to eradicate C hepatitis virus after well conducted treatment
The liver biopsy should have been realised at least 18 months before inclusion :

Either before treatment for C hepatitis in patients treated at most 7 months Or at least 6 months after anti HCV treatment in patient treated for more than 7 months (wash out period)

Regular follow up in an outpatient clinic for HIV
Unchanged antiretroviral treatment the last 3 months before inclusion
Inform consent

Exclusion Criteria:

History of transplantation or clinical hepatic failure
Opportunistic infection in the past three months before inclusion
Any hepatic disease not related to HCV (B hepatitis, hemochromatosis, Wilson disease)
Diabetes mellitus
Immunocompromised treatment
Active intravenous drug addiction
Alcohol consumption of more than 50 g per day
Counterindication for the use of interferon

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: NCT00122616

Locations


France
Service de Maladies Infectieuses et de Réanimation Médicale
Rennes, France, 35033

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Hoffmann-La Roche

Investigators


Principal Investigator:	Jean Marc Chapplain, MD	Hopital Pontchaillou Rennes
Study Chair:	Eric Belissant, MD	CIC Hôpital Pontchaillou Rennes

More Information

No publications provided by French National Agency for Research on AIDS and Viral Hepatitis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chapplain JM, Bellissant E, Guyader D, Molina JM, Poizot-Martin I, Perré P, Pialoux G, Turlin B, Mouchel C, Renault A, Michelet C; ANRS HC-12 Study Group. The effects of a maintenance therapy with peg-interferon alpha-2a on liver fibrosis in HIV/HCV co-infected patients: a randomized controlled trial. J Infect. 2013 Oct;67(4):313-21. doi: 10.1016/j.jinf.2013.05.007. Epub 2013 Jun 22.


Responsible Party:	French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:	NCT00122616 History of Changes
Other Study ID Numbers:	ANRSHC12 FIBROSTOP
Study First Received:	July 19, 2005
Last Updated:	February 21, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:


HIV infections peginterferon alfa-2a Treatment Failure Hepatitis C, Chronic Treatment Experienced

Additional relevant MeSH terms:


Hepatitis Hepatitis C Hepatitis C, Chronic Digestive System Diseases Flaviviridae Infections Hepatitis, Chronic Hepatitis, Viral, Human Liver Diseases RNA Virus Infections Virus Diseases Interferon-alpha	Peginterferon alfa-2a Ribavirin Anti-Infective Agents Antimetabolites Antiviral Agents Immunologic Factors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015