High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3 (DARGEN-3)

Dr. Conrado Fernandez

Status and phase: Completed; Phase 4

Conditions: Chronic Hepatitis C

Treatments: Drug: Peginterferon alfa 2 A; Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta; Drug: Peginterferon alfa 2; Drug: ribavirin

Study type: Interventional

Funder types: Other

Identifiers

NCT00830609

ROCHE FARMA S.A.

Details and patient eligibility

About

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.

Full 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.

Enrollment: 101 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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101 participants in 3 patient groups

A

Active Comparator group

Description:

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

Treatment:

Drug: ribavirin

Drug: ribavirin

Drug: ribavirin

Drug: Peginterferon alfa 2 A

B1

Experimental group

Description:

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.

Treatment:

Drug: ribavirin

Drug: Peginterferon alfa 2

Drug: ribavirin

Drug: ribavirin

Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta

Drug: Peginterferon alfa 2 A

B2

Experimental group

Description:

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.

Treatment:

Drug: ribavirin

Drug: ribavirin

Drug: ribavirin

Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta

Drug: Peginterferon alfa 2 A