High Dose Ribavirin in the Treatment of Chronic Hepatitis C
Prospective, Open-label, Randomised Controlled Trial on Efficacy and Tolerability of PegIFN-alpha 2a + Serum Level-adapted RBV vs. PegIFN-alpha 2a + Weight-based RBV in Treatment-naive Patients With Chronic Hepatitis C Genotype 1
3 other identifiers
interventional
32
1 country
5
Brief Summary
Treatment of patients with chronic hepatitis C infected with genotype 1 hepatitis C virus (HCV) consists of combined peginterferon/ribavirin for 48 weeks. Approximately 50% of patients experience sustained virological response which equals cure. All other patients either do not respond or experience recurrence of HCV virus and chronic hepatitis. Important predictors of successful treatment are sustained dosing of both peginterferon and ribavirin. With regard to the latter, clinical evidence indicates that higher ribavirin doses may in fact even improve treatment outcome. However, high ribavirin doses cause hemolytic anemia which require dose reductions. Recent clinical experience show that erythropoetic growth factors, including erythropoetin, can counteract hemolytic anemia caused by antiviral treatment in chronic hepatitis C patients. Therefore, the current trial aims to test whether higher ribavirin doses adapted to a target plasma concentrations instead of a weight-based dosing result in better healing rates, and whether ribavirin-associated hemolytic anemia can be compensated by concommitant erythropoetin treatment. Using a randomized, controlled, open-label design, the investigators hypothesize that patients with high ribavirin doses adapted to plasma levels experience better viral clearance than patients treated with standard weight-based ribavirin doses. In addition, the investigators hypothesize that erythropoetin treatment will counteract hemolytic anemia induced by ribavirin thereby allowing maintenance of target plasma concentrations without ribavirin dose reductions.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2007
Typical duration for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2007
CompletedFirst Submitted
Initial submission to the registry
July 17, 2009
CompletedFirst Posted
Study publicly available on registry
July 23, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2011
CompletedNovember 11, 2011
November 1, 2011
3.4 years
July 17, 2009
November 10, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Sustained virological response
1 Day
Secondary Outcomes (3)
Adverse Events
day 1 until 24 weeks after end or treatment
Rapid virological response at 4 weeks of treatment
4 weeks
Early virological response at 12 weeks of treatment
12 weeks
Study Arms (2)
A
EXPERIMENTALPegIFN-alpha 2a + RBV (commenced according to kidney function) adjusted to plasma levels. Treatment with erythropoetin 3x3,000IU/week up to 3x10,000IU/week in case of hemolytic anemia
B
ACTIVE COMPARATORPegIFN-alpha 2a + RBV (weight based; 1,000 or 1,200 mg/day)
Interventions
Ribavirin dose started according to kidney function (usually 1,800mg) and adapted according to plasma level during follow-up
Ribavirin dose started at 1,000mg (body weight \<65kg) or 1,200mg (body weight equal or \>65kg)
Eligibility Criteria
You may qualify if:
- Male and female patients aged 18-65 years
- Elevated liver enzymes levels
- Compensated liver disease
- Available liver histology confirming METAVIR F2 fibrosis
- Written consent to participation
You may not qualify if:
- Age \<18, \>65
- Prior ribavirin treatment
- Intolerance towards ribavirin, PegIFN or erythropoetin
- Pregnancy or breast feeding
- Relevant cardiovascular or pulmonary disease
- Kidney insufficiency (creatinine clearance \<50ml/min)
- Coinfection with HIV or hepatitis B virus
- Hepatic comorbidities (hemochromatosis, Wilson's disease, autoimmune disorders)
- Alcohol consumption \> 40g/day
- Psychiatric disorders
- Malignancy (except for basalioma)
- Active consumption of illicit drugs
- Lack of consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Bernlead
- Roche Pharma AGcollaborator
- University of Lausannecollaborator
- Cantonal Hospital of St. Gallencollaborator
- Waid City Hospital, Zurichcollaborator
- University of Baselcollaborator
Study Sites (5)
Dept of Gastroenterology, University of Basel
Basel, CH-4031, Switzerland
Institute of Clinical Pharmacology and Visceral Research, University of Bern
Bern, CH-3010, Switzerland
Division of Gastroenterology, University of Lausanne
Lausanne, CH-1011, Switzerland
Kantonsspital St.Gallen
Sankt Gallen, CH-9007, Switzerland
Stadtspital Waid, Zürich
Zurich, Ch-8037, Switzerland
Related Publications (1)
Pfaundler N, Kessebohm K, Blum R, Stieger M, Stickel F. Adding pancreatic panniculitis to the panel of skin lesions associated with triple therapy of chronic hepatitis C. Liver Int. 2013 Apr;33(4):648-9. doi: 10.1111/liv.12119. Epub 2013 Feb 15. No abstract available.
PMID: 23410147DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Felix Stickel, MD
Institute for Clinical Pharmacology and Visceral Research, University of Bern
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
July 17, 2009
First Posted
July 23, 2009
Study Start
November 1, 2007
Primary Completion
April 1, 2011
Study Completion
April 1, 2011
Last Updated
November 11, 2011
Record last verified: 2011-11