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

Chronic Hepatitis C Clinical Trial

— DARGEN-3  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00830609
• Other study ID #: ROCHE FARMA S.A.
• Status: Completed
• Phase: Phase 4
• First received: January 27, 2009
• Last updated: March 12, 2012
• Start date: November 2008
• Est. completion date: December 2011

Study information

• Verified date: March 2012
• Source: Hospital Universitario Fundación Alcorcón
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: December 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

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 ß (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
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
RBV 1600 mg/day 24 weeks
• ribavirin
ribavirin 800 mg/day for 24 weeks
• Peginterferon alfa 2
Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks
• ribavirin
RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks

Locations

Country	Name	City	State
Spain	Hospital Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital de Getafe	Getafe	Madrid
Spain	Hospital San Cecilio	Granada
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital de Bellvitge	L´Hospitalet de Llobregat	Barcelona
Spain	Hospital de León	León
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Costa del Sol	Marbella	Málaga
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Parc Taulí	Sabadell	Barcelona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital de Donostia	San Sebastian	Guipuzcoa
Spain	Hospital Marqués de Valdecilla	Santander
Spain	Hospital de Valme	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Santiago Apóstol	Vitoria
Spain	Hospital Clínico de Zaragoza	Zaragoza
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Conrado Fernandez

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.		1 year	Yes
Secondary	Rate of patients with undetectable RNA-HCV in each arm at week 4 and 24 of treatment. Rate of adverse effects in each arm.		1 year	Yes