High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3

NCT ID: NCT00830609

Last Updated: 2012-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2011-12-31

Brief Summary

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.

Detailed Description

Aims:

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

2. 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 at week 4, standard of care will be continued (Peginterferon α-2a, 180 μg/wee plus Ribavirin (800 mg/day) over 20 additional weeks).

B2.- If RNA-HCV were detectable at week 4, 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.

Conditions

Chronic Hepatitis C

Study Design

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

Study Groups

A

Patients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks).

Group Type: ACTIVE_COMPARATOR

Peginterferon alfa 2 A

Intervention Type: DRUG

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)

ribavirin

Intervention Type: DRUG

ribavirin 800 mg/day for 24 weeks

B1

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.

Group Type: EXPERIMENTAL

Peginterferon alfa 2 A

Intervention Type: DRUG

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)

Peginterferon alfa 2 A, ribavirin + Epo Beta

Intervention Type: DRUG

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

Peginterferon alfa 2

Intervention Type: DRUG

Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks

ribavirin

Intervention Type: DRUG

RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks

B2

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.

Group Type: EXPERIMENTAL

Peginterferon alfa 2 A

Intervention Type: DRUG

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)

Peginterferon alfa 2 A, ribavirin + Epo Beta

Intervention Type: DRUG

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

ribavirin

Intervention Type: DRUG

RBV 1600 mg/day 24 weeks

Interventions

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)

Intervention Type: 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

Intervention Type: DRUG

ribavirin

RBV 1600 mg/day 24 weeks

Intervention Type: DRUG

ribavirin

ribavirin 800 mg/day for 24 weeks

Intervention Type: DRUG

Peginterferon alfa 2

Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks

Intervention Type: DRUG

ribavirin

RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks

Intervention Type: DRUG

Other Intervention Names

Pegasys; Pegasys; peginterferon alfa 2 a; Epoetin beta; Pegasys; Pegasys; Pegasys

Eligibility 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(Eg, thalassemia, 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 cardiopathy grave.
• Advanced atherosclerosis
• Solid organ or bone marrow transplant.

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

Sponsors

Dr. Conrado Fernandez

OTHER

Sponsor Role: lead

Responsible Party

Dr. Conrado Fernandez

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Conrado M Fernandez-Rodriguez

Role: STUDY_DIRECTOR

Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.

Locations

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital del Mar

Barcelona, Barcelona, Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, Barcelona, Spain

Hospital de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Parc Taulí

Sabadell, Barcelona, Spain

Hospital Marqués de Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Reina Sofía

Córdoba, Córdoba, Spain

Hospital Universitario Virgen de las Nieves

Granada, Granada, Spain

Hospital San Cecilio

Granada, Granada, Spain

Hospital de Donostia

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital de León

León, León, Spain

Hospital Fundación Alcorcón

Alcorcón, Madrid, Spain

Hospital de Getafe

Getafe, Madrid, Spain

Hospital La Princesa

Madrid, Madrid, Spain

Hospital Gregorio Marañon

Madrid, Madrid, Spain

Hospital 12 de Octubre

Madrid, Madrid, Spain

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Hospital Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Costa del Sol

Marbella, Málaga, Spain

Hospital Clínico Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Hospital Central de Asturias

Oviedo, Oviedo, Spain

Hospital Clinico Universitario de Salamanca

Salamanca, Salamanca, Spain

Hospital de Valme

Seville, Sevilla, Spain

Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Hospital Clínico Universitario de Valladolid

Valladolid, Valladolid, Spain

Hospital Santiago Apóstol

Vitoria-Gasteiz, Vitoria, Spain

Hospital Clínico de Zaragoza

Zaragoza, Zaragoza, Spain

Hospital Miguel Servet

Zaragoza, Zaragoza, Spain

Countries

Spain

References

Fernandez-Rodriguez CM, Morillas RM, Masnou H, Navarro JM, Barcena R, Gonzalez JM, Martin-Martin L, Poyato A, Miquel-Planas M, Jorquera F, Casanovas T, Salmeron J, Calleja JL, Sola R, Alonso S, Planas R, Romero-Gomez M. Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study. Gastroenterol Hepatol. 2014 Jan;37(1):1-8. doi: 10.1016/j.gastrohep.2013.10.005. Epub 2013 Dec 17.

Reference Type: DERIVED

PMID: 24360571 (View on PubMed)

Other Identifiers

ROCHE FARMA S.A.

Identifier Type: -

Identifier Source: org_study_id