High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3
- Conditions
- Chronic Hepatitis C
- Interventions
- Drug: Peginterferon alfa 2 A, ribavirin + Epo BetaDrug: Peginterferon alfa 2
- Registration Number
- NCT00830609
- Lead Sponsor
- Dr. Conrado Fernandez
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- HCV Genotype 3
- RNA-HCV > > 600.000 IU/ml.
- Compromise to use contraceptive measures on treatment until 6 months after the end of treatment.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A Peginterferon alfa 2 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). A ribavirin Patients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks). B1 Peginterferon alfa 2 A, ribavirin + Epo Beta 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. B1 Peginterferon alfa 2 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. B2 Peginterferon alfa 2 A, ribavirin + Epo Beta 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. B1 Peginterferon alfa 2 A 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. B2 Peginterferon alfa 2 A 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. B1 ribavirin 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. B2 ribavirin 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.
- Primary Outcome Measures
Name Time Method Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment. 1 year
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (28)
Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Costa del Sol
🇪🇸Marbella, Málaga, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Spain
Hospital Santiago Apóstol
🇪🇸Vitoria, Spain
Hospital Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital de Valme
🇪🇸Sevilla, Spain
Hospital de Bellvitge
🇪🇸L´Hospitalet de Llobregat, Barcelona, Spain
Hospital de Donostia
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Hospital Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Hospital Fundación Alcorcón
🇪🇸Alcorcón, Madrid, Spain
Hospital de Getafe
🇪🇸Getafe, Madrid, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Hospital San Cecilio
🇪🇸Granada, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital de León
🇪🇸León, Spain
Hospital La Princesa
🇪🇸Madrid, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸Valladolid, Spain
Hospital Clínico de Zaragoza
🇪🇸Zaragoza, Spain
Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Clínico Universitario Virgen de la Victoria
🇪🇸Málaga, Spain