High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3 (DARGEN-3)
This study has been completed.
Sponsor:
Dr. Conrado Fernandez
Information provided by (Responsible Party):
Dr. Conrado Fernandez, Hospital Universitario Fundación Alcorcón.
ClinicalTrials.gov Identifier:
NCT00830609
First received: January 27, 2009
Last updated: March 12, 2012
Last verified: March 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Hepatitis C |
Drug: Peginterferon alfa 2 A Drug: Peginterferon alfa 2 A, ribavirin + Epo Beta Drug: ribavirin Drug: Peginterferon alfa 2 |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Hospital Universitario Fundación Alcorcón.:
Primary Outcome Measures:
- Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Rate of patients with undetectable RNA-HCV in each arm at week 4 and 24 of treatment. Rate of adverse effects in each arm. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
| Enrollment: | 101 |
| Study Start Date: | November 2008 |
| Study Completion Date: | December 2011 |
| Primary Completion Date: | September 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 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).
|
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 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)
Other Name: Pegasys
Drug: ribavirin
ribavirin 800 mg/day for 24 weeks
Other Name: Pegasys
|
|
Experimental: 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.
|
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 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)
Other Name: Pegasys
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
Other Name: Pegasys
Drug: Peginterferon alfa 2
Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks
Other Name: Pegasys
Drug: ribavirin
RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks
Other Name: Pegasys
|
|
Experimental: 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.
|
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 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)
Other Name: Pegasys
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
Other Name: Pegasys
Drug: ribavirin
RBV 1600 mg/day 24 weeks
Other Names:
|
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.
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.
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00830609
Locations
| Spain | |
| Hospital Germans Trias i Pujol | |
| Badalona, Barcelona, Spain, 08916 | |
| Hospital de Bellvitge | |
| L´Hospitalet de Llobregat, Barcelona, Spain, 08907 | |
| Hospital Parc Taulí | |
| Sabadell, Barcelona, Spain, 08208 | |
| Hospital de Donostia | |
| San Sebastian, Guipuzcoa, Spain, 20014 | |
| Hospital Fundación Alcorcón | |
| Alcorcón, Madrid, Spain, 28922 | |
| Hospital de Getafe | |
| Getafe, Madrid, Spain, 28901 | |
| Hospital Puerta de Hierro | |
| Majadahonda, Madrid, Spain, 28222 | |
| Hospital Costa del Sol | |
| Marbella, Málaga, Spain, 29603 | |
| Hospital Clinic i Provincial de Barcelona | |
| Barcelona, Spain, 08036 | |
| Hospital del Mar | |
| Barcelona, Spain, 08003 | |
| Hospital Universitario Reina Sofía | |
| Córdoba, Spain, 14004 | |
| Hospital Universitario Virgen de las Nieves | |
| Granada, Spain, 18004 | |
| Hospital San Cecilio | |
| Granada, Spain | |
| Hospital de León | |
| León, Spain, 24071 | |
| Hospital Ramón y Cajal | |
| Madrid, Spain, 28034 | |
| Hospital La Princesa | |
| Madrid, Spain, 28006 | |
| Hospital 12 de Octubre | |
| Madrid, Spain, 28021 | |
| Hospital Gregorio Marañon | |
| Madrid, Spain, 28007 | |
| Hospital Clínico Universitario Virgen de la Victoria | |
| Málaga, Spain, 29010 | |
| Hospital Central de Asturias | |
| Oviedo, Spain, 33006 | |
| Hospital Clinico Universitario de Salamanca | |
| Salamanca, Spain, 37007 | |
| Hospital Marqués de Valdecilla | |
| Santander, Spain, 39008 | |
| Hospital de Valme | |
| Sevilla, Spain, 41014 | |
| Hospital Clínico Universitario de Valencia | |
| Valencia, Spain, 46010 | |
| Hospital Clínico Universitario de Valladolid | |
| Valladolid, Spain, 47005 | |
| Hospital Santiago Apóstol | |
| Vitoria, Spain, 01004 | |
| Hospital Miguel Servet | |
| Zaragoza, Spain, 50009 | |
| Hospital Clínico de Zaragoza | |
| Zaragoza, Spain, 50009 | |
Sponsors and Collaborators
Dr. Conrado Fernandez
Investigators
| Study Director: | Conrado M Fernandez-Rodriguez | Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos. |
More Information
No publications provided
| Responsible Party: | Dr. Conrado Fernandez, MD, Hospital Universitario Fundación Alcorcón. |
| ClinicalTrials.gov Identifier: | NCT00830609 History of Changes |
| Other Study ID Numbers: | ROCHE FARMA S.A. |
| Study First Received: | January 27, 2009 |
| Last Updated: | March 12, 2012 |
| Health Authority: | Spain: Spanish Agency of Medicines |
Keywords provided by Hospital Universitario Fundación Alcorcón.:
|
Chronic Hepatitis C Genotype 3 High viral load |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis, Chronic Hepatitis C Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections |
Flaviviridae Infections Ribavirin Peginterferon alfa-2a Interferon-alpha Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antimetabolites Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 19, 2013