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

This study has been completed.
Sponsor:
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
  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:
  • peginterferon alfa 2 a
  • ribavirin
  • Epoetin beta

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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 by Hospital Universitario Fundación Alcorcón.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 July 20, 2014