High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3 - Full Text View

Sponsored by:	Hospital Universitario Fundación Alcorcón.
Information provided by:	Hospital Universitario Fundación Alcorcón.
ClinicalTrials.gov Identifier:	NCT00830609

Purpose

The rate of sustained virological response (SVR) in patients with chronic hepatitis C, genotype 3, high viral load and without rapid virological response (RNA-HCV negative at week 4) is low. Standard of care of these patients include treatment with weekly peginterferon plus 800 mg/day of ribavirin (RBV).

Extended treatment to 48 weeks does not provide more clinical benefit than the standard duration. The main hypothesis is that higher dose of ribavirin may be better in terms of SVR than the standard dose.

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: Peginterferon alfa 2 A Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta Drug: ribavirin Drug: Peginterferon alfa 2	Phase IV

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2a

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Effect of High Dose vs. Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3, High Viral Load Without Rapid Virological Response

Further study details as provided by Hospital Universitario Fundación Alcorcón.:

Primary Outcome Measures:

Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Rate of patients with undetectable RNA-HCV in each arm at week 4 and 24 of treatment. Rate of adverse effects in each arm. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	111
Study Start Date:	November 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Patients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks).	Drug: Peginterferon alfa 2 A Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 800 mg/day po (Control Group) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epoetin β (450 IU/kg/week) SC over 4 weeks (Arm B1) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epo beta 450 UI over four weeks (Arm B1) If RNA-HCV positive at week 4, Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day plus Epo beta 450 UI to keep Hb>12 g/dL if required over 20 additional weeks (Arm B2) Drug: ribavirin ribavirin 800 mg/day for 24 weeks
B1: Experimental After a period of 4 weeks with peginterferon alfa 2 a 180 mcg/week plus RBV 1600 mg/day (Induction phase), these patients will be allocated according to negativity or positivity of RNA-HCV at week 4. If RNA-HCV negative, treatment with peginterferon alfa 2 a 180 mcg/week plus RBV 800 mg/day (SOC) will be continued over 20 additional weeks (Arm B1). Epo β (450 IU/kg/week) will be administered as required to maintain hemoglobin > 12g/dL.	Drug: Peginterferon alfa 2 A Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 800 mg/day po (Control Group) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epoetin β (450 IU/kg/week) SC over 4 weeks (Arm B1) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epo beta 450 UI over four weeks (Arm B1) If RNA-HCV positive at week 4, Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day plus Epo beta 450 UI to keep Hb>12 g/dL if required over 20 additional weeks (Arm B2) Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta Ribavirin 1,600 mg/day plus peginterferon alfa 2A 180 mcg/week plus Epo beta 450 IU/Kg/day to maintain Hb>12g/dl over 4 or 24 weeks Drug: Peginterferon alfa 2 Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks Drug: ribavirin RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks
B2: Experimental If RNA-HCV at week 4 remains positive after the induction phase, then peginterferon alfa 2 a 180 mcg/week plus RBV 1600 mg/day will be continued for 20 additional weeks (Arm B2). Epo β (450 IU/kg/week) will be administered as required to maintain hemoglobin > 12g/dL.	Drug: Peginterferon alfa 2 A Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 800 mg/day po (Control Group) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epoetin β (450 IU/kg/week) SC over 4 weeks (Arm B1) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epo beta 450 UI over four weeks (Arm B1) If RNA-HCV positive at week 4, Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day plus Epo beta 450 UI to keep Hb>12 g/dL if required over 20 additional weeks (Arm B2) Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta Ribavirin 1,600 mg/day plus peginterferon alfa 2A 180 mcg/week plus Epo beta 450 IU/Kg/day to maintain Hb>12g/dl over 4 or 24 weeks Drug: ribavirin RBV 1600 mg/day 24 weeks

Detailed Description:

Aims:

Efficacy 1.1) Rate of RNA-HCV negative at week 4 and 24 in each arm. 1.2) Rate of SVR in each arm.
Safety 2.1) Rate of adverse effects in each arm.

Design: Randomized controlled trial.

Patients will be randomly allocated into three arms:

Arm A : Peginterferon α-2a (180 μg/week)SC. plus Ribavirin (800 mg/day) p.o. over 24 weeks.

Arm B: Peginterferon α-2a (180 μg/week) plus Ribavirin (1600 mg/day) with support of Epoetin β (450 IU/kg/week) SC over 4 weeks:

B1.- If RNA-HCV undetectable in week, standard of care will be continued (Peginterferon α-2a (180 μg/week)plus Ribavirin (800 mg/day) over 20 additional weeks. B2.- If RNA-HCV were detectable at week 4 ARN-VHC, treatment will be continued with peginterferon α-2a (180 μg/week) plus RBV(1,600 mg/day) plus Epoetin β (450 UI/kg/week) over 20 additional weeks.

Sample size: 111 patients. To increase the SVR from 50% to 75%. Beta: 0.1; alfa: 0.05; Loss: 15%.

Randomization will be 1:2, 37 patients in Group A and 74 patients in group B.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HCV Genotype 3
RNA-HCV > > 600.000 IU/ml.
Compromise to use contraceptive measures on treatment until 6 months after the end of treatment.

Exclusion Criteria:

Pregnant or breastfeeding females.
Concurrent treatment with antineoplastic or immunomodulatory agents, including corticosteroids or radiation therapy over the last 6 months before starting the trial
Treatment with investigational drugs < 6 weeks before starting the trial
Chronic liver disease other than hepatitis C.
Evidence of hepatocellular carcinoma.
Evidence of carcinoma hepatocellular
Decompensated liver disease
Baseline Neutrophil count < 1500/cc; or Platelet count < 90,000/cc
Baseline Hemoglobin <12 g/dL in females o <13 g/dL in males.
Increased risk of anemia Pacientes con riesgo basal aumentado de anemia (Eg, talasemia, spherocytosis..).
Ischemic heart disease or cerebrovascular disease.
Serum creatinine >1.5 times upper limit of normality.
History of severe psychiatric conditions (Major antidepressives or neuroleptic drugs required for major depression or psychosis), suicide attempts or psychiatric disability .
History of convulsive disorders.
Immunological conditions.
Chronic Obstructive Lung Disease with limited functionality
Severe heart disease or congestive cardiac insufficiency cardiopatía grave.
Advanced atherosclerosis
Solid organ or bone marrow transplant.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00830609

Contacts

Contact: Conrado M Fernandez-Rodriguez, MD

+34 91 621 97 05

cfernandez@fhalcorcon.es

Locations

Spain
Hospital San Cecilio	Recruiting
Granada, Spain
Contact: Javier Salmerón fsalmeronescobar@sepd.es
Principal Investigator: Javier Salmeron

Sponsors and Collaborators

Hospital Universitario Fundación Alcorcón.

Investigators

Study Director:

Conrado M Fernandez-Rodriguez

Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.

More Information

No publications provided

Responsible Party:	Hospital Universitario Fundación Alcorcón ( Conrado Fernández )
Study ID Numbers:	ROCHE FARMA S.A.
Study First Received:	January 27, 2009
Last Updated:	January 28, 2009
ClinicalTrials.gov Identifier:	NCT00830609 History of Changes
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Hospital Universitario Fundación Alcorcón.:

Chronic Hepatitis C
Genotype 3
High viral load

Study placed in the following topic categories:

Antimetabolites
Interferon-alpha
Epoetin Alfa
Liver Diseases
Hepatitis, Chronic
Interferons
Ribavirin
Benzocaine
Hepatitis, Viral, Human

Angiogenesis Inhibitors
Antiviral Agents
Hepatitis
Virus Diseases
Digestive System Diseases
Peginterferon alfa-2a
Hepatitis C
Interferon Alfa-2a
Hepatitis C, Chronic

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Liver Diseases
Flaviviridae Infections
Hepatitis, Chronic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Ribavirin
Physiological Effects of Drugs
Hepatitis, Viral, Human
Therapeutic Uses
Hepatitis C
Angiogenesis Modulating Agents

Growth Inhibitors
RNA Virus Infections
Growth Substances
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Virus Diseases
Hepatitis
Digestive System Diseases
Peginterferon alfa-2a
Interferon Alfa-2a
Hepatitis C, Chronic

ClinicalTrials.gov processed this record on May 06, 2009