Clinical trial NCT00351403: Individually Adapted Therapy Duration for the Treatment of Chronic Hepatitis C Genotype 1 Infection
Official title: Individually Adapted Therapy Duration From 24 to 72 Weeks for the Treatment of a Chronic Hepatitis C Genotype 1 Infection With Peginterferon Alfa-2b Plus Ribavirin in Dependence of the Initial Concentration and the Decline of the HCV RNA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C, Chronic
Keywords: Chronic HCV infection
Genotype 1
Individually adapted therapy
Peginterferon alfa-2b
Ribavirin
Sustained viral response (SVR)
Lead sponsor: FGK Clinical Research GmbH
Sponsor class: INDUSTRY
Collaborators: name: University Hospital, Saarland
First posted: 2006-07-12
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Sustained viral response (HCV RNA negativity 24 weeks after end of treatment)
Secondary outcomes:
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Medizinische Universitätsklinik Freiburg
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: Universitätsklinik Heidelberg
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Uniklinikum Erlangen
state: Bayern
city: München
country: Germany
facility: Klinikum Großhadern
state: Bayern
city: München
country: Germany
facility: Technische Universität München
state: Bayern
city: Würzburg
country: Germany
facility: Klinikum der Universität Würzburg
state: Bayern
city: Frankfurt
country: Germany
facility: Klinikum der J.W.-Goethe-Universität
state: Hessen
city: Frankfurt
country: Germany
facility: Praxis für Innere Medizin
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Bochum
country: Germany
facility: St. Josef-Hospital
state: Nordrhein-Westfalen
city: Dusseldorf
country: Germany
facility: Gemeinschaftspraxis
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Medizinische Universitäts-Klinik Essen
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Universität zu Köln
state: Nordrhein-Westfalen
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
state: Nordrhein.Westfalen
city: Mainz
country: Germany
facility: Universitätsklinikum der J. Gutenberg Universität
state: Rheinland-Pfalz
city: Homburg / Saar
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Kiel
country: Germany
facility: Christian-Albrechts-Universität zu Kiel
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Hepatologische Schwerpunktpraxis
city: Berlin
country: Germany
facility: Charité, Campus Virchow-Klinikum
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
Study officials:
affiliation: University Hospital, Saarland
name: Christoph Sarrazin, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.