Effect of High Dose vs. Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3, High Viral Load Without Rapid Virological Response
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 101
- Locations
- 28
- Primary Endpoint
- Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.
Study Overview
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:
- 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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).
Intervention: Peginterferon alfa 2 A (Drug)
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).
Intervention: ribavirin (Drug)
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.
Intervention: Peginterferon alfa 2 A (Drug)
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.
Intervention: Peginterferon alfa 2 A, ribavirin + Epo Beta (Drug)
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.
Intervention: Peginterferon alfa 2 (Drug)
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.
Intervention: ribavirin (Drug)
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.
Intervention: Peginterferon alfa 2 A (Drug)
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.
Intervention: Peginterferon alfa 2 A, ribavirin + Epo Beta (Drug)
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.
Intervention: ribavirin (Drug)
Outcomes
Primary Outcomes
Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.
Time Frame: 1 year
Secondary Outcomes
- 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)
Investigators
Dr. Conrado Fernandez
MD
Hospital Universitario Fundación Alcorcón