Clinical trial NCT00356486: Viral Kinetics of Treatment With Peginterferon Alpha-2a, Ribavirin and Epoetin β in Patients Coinfected HCV/HIV
Official title: Open, Multicentre and Randomised Phase IV Study to Evaluate Viral Kinetics in the First 12 Weeks of Patients With Chronic Hepatitis C Genotypes 1 and 4 Coinfected by the Human Immunodeficiency Virus Treated With Induction Doses of Peginterferon Alpha-2a (40 KD) (270 μg/Week) and Ribavirin (1600 mg/Day) With Epoetin β Support (450 IU/kg/Week)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Chronic Hepatitis C
Co-infection
Induction dose
HIV
HIV Infections
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2006-07-26
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the early virological response (EVR = undetectable \[ribonucleic acid-hepatitis C virus\] RNA-HCV or a reduction of \> 2 log10) of patients with chronic hepatitis C coinfected with HIV treated with induction doses of peginterferon alpha-2a (40 KD) 270 µg/week and ribavirin 1600 mg/day for 4 weeks, followed by 8 weeks of treatment with peginterferon alpha-2a (40 KD) 180 µg/week and ribavirin 1000-1200 mg/day versus treatment with peginterferon alpha-2a (40 KD) 180 µg/week and ribavirin 1000-1200 mg/day for 12 weeks.

Detailed description: This study seeks to ascertain whether treatment with higher doses of PEGASYS (270 µg/week) and ribavirin (1600 mg/day) for the first four weeks achieves the plasma concentrations of the product in the blood needed to reduce the half-life of the virions and accelerate the elimination thereof. This would bring the viral kinetic curves in coinfected patients closer to the model described for mono-infected HCV patients, probably achieving improved rates of response in week 12 (early virological response) and posterior in week 72 (sustained virological response).

Therefore, the patients were randomised to treatment with two different doses, 270 µg and 180 µg of PEGASYS, and 1600 mg and 1000-1200 mg of ribavirin.

Eligibility criteria: Inclusion Criteria:

* Serological evidence of chronic hepatitis C infection in an anti-HCV antibody test
* Detectable RNA-HCV plasma level genotype 1 and 4
* ALT serum activity above the upper limit of normality
* Chronic liver disease consistent with chronic hepatitis C infection in a biopsy obtained during the two years prior to inclusion in the study
* Serological evidence of HIV-1 infection, diagnosed by Enzyme-Linked Immunosorbent Assay (ELISA) and confirmed by Western-blot.
* Patients with CD4 cell count \> 200 /µl
* Stable status in HIV-1 infection, in the investigator's opinion, in other words, patients that are not expected to progress during the study.
* Patients treated with stable anti-retroviral therapy (HAART), which does not include nucleoside analogues, for at least 6 weeks before the baseline assessment
* Patients that do not receive HAART therapy
* Negative pregnancy test in urine or blood

Exclusion Criteria:

* Women currently pregnant or in the lactation period.
* Patients whose companion is pregnant.
* Therapy with interferon (IFN) or ribavirin at any previous time.
* Patients with cirrhosis in the hepatic biopsy.
* Documented suspicion by ultrasound of hepatocarcinoma.

Primary outcomes:
measure: Percentage of patients with undetectable RNA-HCV
timeFrame: at week 12 after starting treatment
Secondary outcomes:
measure: Variations of the levels of RNA-HCV
timeFrame: from baseline until weeks 4, 8, and 12 of the study
measure: Percentage of patients with undetectable HCV RNA
timeFrame: in weeks 4 and 8 of the study
measure: Levels of ALT
timeFrame: At weeks 4, 8, and 12
measure: Percentage of patients that must reduce the dose of peginterferon alpha-2a (40 KD) and ribavirin.
timeFrame: During the 12 weeks of follow-up
measure: Percentage of patients that drop out of the study for adverse effects or intolerance
timeFrame: During the 12 weeks of follow-up
measure: Variations in levels of haemoglobin, neutrophil, and platelet count
timeFrame: at 4, 8, and 12 weeks with regard to baseline
measure: AIDS-defining events or death
timeFrame: During the 12 weeks of follow-up
measure: Changes in the CD4/CD8 cell count
timeFrame: At 4, 8, and 12 weeks of follow-up
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol, Badalona
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Vic
country: Spain
facility: Hospital General de Vic
state: Barcelona
city: San Sebastián
country: Spain
facility: Hospital de Donostia
state: Donostia
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial
city: Cádiz
country: Spain
facility: Hospital Puerta del Mar
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón.
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital La Paz
Study officials:
affiliation: LLuita contra la Sida Foundation-HIV Unit
name: Bonaventura Clotet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: