High Dose Ribavirin in the Treatment of Chronic Hepatitis C

This study has been completed.
Sponsor:
Collaborators:
Roche Pharma AG
University of Lausanne
Cantonal Hospital of St. Gallen
Stadtspital Waid, Zürich, Switzerland
University of Basel
Information provided by:
University of Bern
ClinicalTrials.gov Identifier:
NCT00944684
First received: July 17, 2009
Last updated: November 10, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Drug: High ribavirin dose
Drug: Standard ribavirin dose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Bern:

Primary Outcome Measures:
  • Sustained virological response [ Time Frame: 1 Day ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: day 1 until 24 weeks after end or treatment ] [ Designated as safety issue: Yes ]
  • Rapid virological response at 4 weeks of treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Early virological response at 12 weeks of treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: November 2007
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
PegIFN-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
Drug: High ribavirin dose
Ribavirin dose started according to kidney function (usually 1,800mg) and adapted according to plasma level during follow-up
Active Comparator: B
PegIFN-alpha 2a + RBV (weight based; 1,000 or 1,200 mg/day)
Drug: Standard ribavirin dose
Ribavirin dose started at 1,000mg (body weight <65kg) or 1,200mg (body weight equal or >65kg)

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • 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

Exclusion Criteria

  • 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
  • Participation in another trial shorter than 3 months prior to inclusion
  • Lack of consent
  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: NCT00944684

Locations
Switzerland
Dept of Gastroenterology, University of Basel
Basel, Switzerland, CH-4031
Institute of Clinical Pharmacology and Visceral Research, University of Bern
Bern, Switzerland, CH-3010
Division of Gastroenterology, University of Lausanne
Lausanne, Switzerland, CH-1011
Kantonsspital St.Gallen
St. Gallen, Switzerland, CH-9007
Stadtspital Waid, Zürich
Zürich, Switzerland, Ch-8037
Sponsors and Collaborators
University of Bern
Roche Pharma AG
University of Lausanne
Cantonal Hospital of St. Gallen
Stadtspital Waid, Zürich, Switzerland
University of Basel
Investigators
Principal Investigator: Felix Stickel, MD Institute for Clinical Pharmacology and Visceral Research, University of Bern
  More Information

No publications provided by University of Bern

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Felix Stickel, University of Bern, Switzerland
ClinicalTrials.gov Identifier: NCT00944684     History of Changes
Other Study ID Numbers: 091/07, ML21071, SASL-24
Study First Received: July 17, 2009
Last Updated: November 10, 2011
Health Authority: Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by University of Bern:
Chronic hepatitis C
Antiviral treatment
Ribavirin
Sustained virological response
Hemolytic anemia
Erythropoetin

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014