Phase IV Study to Evaluate the Efficacy/Safety to Extend Treatment and High Dose of Ribavirin in co-Infected Patients

Study Overview
=================
Brief Summary
-----------------
To compare the sustained virological response (SVR = ribonucleic acid (RNA) - hepatitis C virus (HCV) undetectable at week 24 before end the treatment) in chronic hepatitis C patients genotype 1-4 co-infected with HIV-HCV, treated with Peginterferón alfa-2a (40 KD) 180 µg/week and Ribavirin (2000 mg/day during 4 weeks, follow of 1000-1200 mg/day, according to body weight); versus Peginterferón alfa-2a (40 KD) 180 μg/week and Ribavirin (1000-1200 mg/day, according to body weight). To evaluate the impact to extend the treatment with Peginterferon alfa-2a and Ribavirin to week 72, in SVR of these patients with genotypes 1-4 without rapid virological response (RVR = RNA - HCV undetectable at 4 week).

Detailed Description
-----------------
The PRESCO study (ribavirin dose 1000-1200 mg/day) emphasized that optimal ribavirin exposure seems to be crucial to maximize sustained virological response and minimize the incidence of relapses after treatment discontinuations. Recent reports showed that it is beneficial to extend the treatment duration in patients without rapid virological response at 4 weeks (RNA-HCV < 50 UI/ml).

Official Title
-----------------
Open, Multicentre,Randomized Phase IV Trial to Evaluate Efficacy/Safety to Extend Treatment Duration With Peginterferon Alfa-2a+High Dose of Ribavirin Supporting Epo β in Treatment of CHC in HIV-HCV Patients Who Not Clear Virus at Week 4

Conditions
-----------------
Chronic Hepatitis C

Intervention / Treatment
-----------------
* Drug: ribavirin
* Drug: ribavirin
* Drug: Peginterferon alfa-2a
* Drug: epoetin beta


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients > 18 years of age Serologic evidence of anti-HCV Detectable plasma HCV-RNA Serologic evidence of HIV-1 infection CD4 cell count >/= 250 cell/mm3 Stable status of HIV-1 infection in the opinion of the investigator Patients on stable antiretroviral therapy (HAART) for at least 6 weeks prior to baseline whose HAART regimen (drugs and dosage) is expected to remain unaltered for the first 6 weeks of this study Patients who have not been on HAART for at least 6 weeks prior to randomization who are willing to delay initiation of HAART therapy for at least 6 weeks Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug Willingness to give written informed consent Exclusion Criteria: Women with ongoing pregnancy or breast feeding Male partners of women who are pregnant IFN/ribavirin therapy at any previous time Child Pugh > 6 (Child Pugh B or C) History or conditions consistent with decompensated liver disease Any investigational drug 6 weeks prior to the first dose of study drug (expanded access programs for HIV treatment are allowed) Patients treated with didanosine and/or zidovudine Positive test at anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBeAg History or other evidence of a medical condition associated with chronic liver disease other than HCV Hepatocarcinoma observed in the liver ecography Serum concentrations of ceruloplasmin or alfa1-antitrypsin at screening consistent with an increased risk of metabolic liver disease Active HIV-related opportunistic infection and/or malignancy requiring acute systemic therapy Absolute neutrophil count (ANC) < 1500 cells/mm3 Hgb < 11 g/dL in women or 12 g/dL in men or any patient for whom anemia would be medically problematic Hemoglobinopathy or any other cause of or tendency for hemolysis Platelet count < 50,000 cells/mm3 History of G-CSF, GM-CSF or epo treatment during 3 months prior to the first dose of study drug Serum creatinine level > 1.5 times the upper limit of normal at screening History of severe psychiatric disease, especially depression History of a severe seizure disorder or current anticonvulsant use History of immunologically mediated disease History or other evidence of chronic pulmonary disease associated with functional limitation History of significant cardiac disease that could be worsened by acute anemia History of thyroid disease poorly controlled on prescribed medications Evidence of severe retinopathy History of major organ transplantation with an existing functional graft History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study History of any systemic anti-neoplastic or immunomodulatory treatment 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study Concomitant medication with rifampin/rifampicin, rifabutin, pyrazinamide, isoniazid, gancyclovir, thalidomide, oxymetholone, immunomodulatory treatments and systemic antiviral agents as adjuvant therapy for CHC Drug use within 6 months of 1st dose and excessive alcohol consumption

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Peginterferon alfa-2a 180 mcg/week + ribavirin 2000 mg/day + epoetin beta 450 UI/week | Drug: ribavirin<br>* 2000 mg/day<br>Drug: Peginterferon alfa-2a<br>* Peginterferon alfa-2a 180 mcg/week<br>Drug: epoetin beta<br>* epoetin beta 450 UI/week<br>|
| Active Comparator: 2<br>Peginterferon alfa-2a 180 mcg/week + ribavirin 1000-1200 mg/day | Drug: ribavirin<br>* 1000-1200 mg/day<br>Drug: Peginterferon alfa-2a<br>* Peginterferon alfa-2a 180 mcg/week<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % patients with RNA-HCV < 50 UI/ml |  | 24 weeks after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % patients with RNA-HCV < 50 UI/ml |  | 4 weeks on treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tailoring treatment, high dose of ribavirin, extend treatment duration