Individually Adapted Therapy Duration for the Treatment of Chronic Hepatitis C Genotype 1 Infection

NCT ID: NCT00351403

Last Updated: 2010-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 390 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2010-01-31

Brief Summary

Patients with chronic hepatitis C genotype 1 virus infection are usually treated with Interferon alfa plus Ribavirin over 48 weeks. For some patients this might be too long, for others too short. An individually adapted therapy length from 24 to 72 weeks will be determined in dependence of the initial virus load and the time to HCV RNA negativity.

The primary objective is to compare the cumulative rate of the sustained viral response (SVR) of the patients with the individually adapted therapy duration to the SVR rates of a historic patient collective under the 48 week standard therapy.

Detailed Description

Further objectives of this trial are:

To record the tolerance of the therapy with Peginterferon alfa-2b plus Ribavirin over 72 weeks inclusive the adverse reactions and the withdrawal rates.

To evaluate the biochemical response to the treatment (ALT values during and after the therapy) in comparison to the virological response to the treatment.

To evaluate the validity of the withdrawal rules of this trial at week 12 and 24 in comparison to the 2-log-rule and a qualitative detection of the HCV RNA at week 24 with a detection limit of 50 IU/ml.

To evaluate the impact of the HCV RNA concentration before the therapy, and the HCV kinetic during the therapy on the response to the treatment in the different groups.

To evaluate the impact of the serum concentration of Ribavirin on anaemia and the virological therapy response, as well as the dependence of the serum concentration of Ribavirin on the creatinine clearance in comparison to the body weight.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Individualized therapy

Lengh of therapy depends on time point when no HCV RNA is detectable in blood with Versant HCV Qualitative assay.

Group Type: EXPERIMENTAL

Ribavirin

Intervention Type: DRUG

Rebetol 200 mg: applied as hard capsule

Peginterferon alfa 2b

Intervention Type: DRUG

PegIntron (50/80/100/120/150 microgram): applied by injection

Historical control

48 week standard therapy

Group Type: OTHER

Ribavirin

Intervention Type: DRUG

Rebetol 200 mg: applied as hard capsule

Peginterferon alfa 2b

Intervention Type: DRUG

PegIntron (50/80/100/120/150 microgram): applied by injection

Interventions

Ribavirin

Rebetol 200 mg: applied as hard capsule

Intervention Type: DRUG

Peginterferon alfa 2b

PegIntron (50/80/100/120/150 microgram): applied by injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with a chronic HCV infection (HCV antibodies and HCV RNA positive)
• Presence of a HCV genotype 1 infection
• Presence of a compensated liver disease satisfying following hematological and biochemical minimum criteria: - Hemoglobin value >= 13 g/dl in men, >= 12 g/dl in women - Leukocytes >= 3.000/mm3 or neutrophile granulocytes > 1.500/mm3 - Thrombocytes > 80.000/mm3
• Total bilirubin in the normal range
• Albumin in the normal range
• Serum creatinine in the normal range THS in the normal range
• Exclusion of an autoimmune hepatitis
• Alpha-Fetoprotein in the normal range
• Negative HIV test
• Negativity of Hepatitis B surface antigens (Hbs-Ag)
• Normal or elevated ALT/GTP values at screening
• At known diabetes mellitus or hypertension an ophthalmologic examination must be performed
• Liver biopsy within the last 12 months must confirm the diagnoses of a chronic hepatitis
• A confirmation must be given that sexually active patients practice a save method of contraception during the therapy and 6 (women) to 7 (men) months after the therapy

Exclusion Criteria

• Age < 18 years, > 70 years
• Previous treatment of hepatitis c with (Peg)Interferon alfa or (Peg)Interferon alfa/Ribavirin
• Patients with organ transplantations other than cornea or hair
• Infection with HCV genotype 2,3,4,5 or 6
• Pregnant or nursing women
• Any other reason for the liver disease than chronic hepatitis C
• Suspected hypersensitivity to Interferon, Peginterferon or Ribavirin
• Participation in a clinical trial or treatment with an investigational product 30 days before inclusion in this study
• Patients with any kind of hemoglobinopathy
• Documented liver disease in advanced state Liver cirrhosis Child B and C
• Each known and existing clinical conditions that might challenge the participation or completion of this clinical trial as depressions, psychosis, severe psychiatric diseases, suicide ideations CNS traumata or cramps which need medicamentous treatment
• Relevant cardiovascular dysfunctions in the last 6 months or patients with clinically relevant changes in the ECG
• Insufficiently adjusted diabetes mellitus
• Severe chronic lung diseases (as e.g. COPD)
• Immunologic diseases or autoimmune-diseases or any other disease which demand a longtime treatment with corticosteroids during this clinical trial
• Clinically relevant gout
• Abuse of drugs, alcohol or pharmaceuticals
• Patient with clinically relevant changes of the retina
• Missing ability or willingness to understand the purpose of this study or to give a written consent for participating in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Saarland

OTHER

Sponsor Role: collaborator

FGK Clinical Research GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Universitätsklinikum des Saarlandes

Principal Investigators

Christoph Sarrazin, MD, PhD

Role: STUDY_CHAIR

University Hospital, Saarland

Locations

Medizinische Universitätsklinik Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Universitätsklinik Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Uniklinikum Erlangen

Erlangen, Bavaria, Germany

Klinikum Großhadern

München, Bavaria, Germany

Technische Universität München

München, Bavaria, Germany

Klinikum der Universität Würzburg

Würzburg, Bavaria, Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, City state of Hamburg, Germany

Klinikum der J.W.-Goethe-Universität

Frankfurt am Main, Hesse, Germany

Praxis für Innere Medizin

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Aachen

Aachen, Nordrhein.Westfalen, Germany

St. Josef-Hospital

Bochum, North Rhine-Westphalia, Germany

Universität zu Köln

Cologne, North Rhine-Westphalia, Germany

Gemeinschaftspraxis

Düsseldorf, North Rhine-Westphalia, Germany

Medizinische Universitäts-Klinik Essen

Essen, North Rhine-Westphalia, Germany

Universitätsklinikum der J. Gutenberg Universität

Mainz, Rhineland-Palatinate, Germany

Universitätsklinikum des Saarlandes

Homburg / Saar, Saarland, Germany

Universitätsklinikum Leipzig

Leipzig, Saxony, Germany

Christian-Albrechts-Universität zu Kiel

Kiel, Schleswig-Holstein, Germany

Hepatologische Schwerpunktpraxis

Berlin, State of Berlin, Germany

Charité, Campus Virchow-Klinikum

Berlin, State of Berlin, Germany

Countries

Germany

References

Sarrazin C, Schwendy S, Moller B, Dikopoulos N, Buggisch P, Encke J, Teuber G, Goeser T, Thimme R, Klinker H, Boecher WO, Schulte-Frohlinde E, Prinzing R, Herrmann E, Zeuzem S, Berg T. Improved responses to pegylated interferon alfa-2b and ribavirin by individualizing treatment for 24-72 weeks. Gastroenterology. 2011 Nov;141(5):1656-64. doi: 10.1053/j.gastro.2011.07.019. Epub 2011 Jul 22.

Reference Type: DERIVED

PMID: 21784046 (View on PubMed)

Other Identifiers

2006-000358-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INDIV-2

Identifier Type: -

Identifier Source: org_study_id