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

Sponsor
Dr. Conrado Fernandez (Other)
Overall Status
Completed
CT.gov ID
NCT00830609
Collaborator
(none)
101
Enrollment
28
Locations
3
Arms
37
Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Nov 1, 2008
Actual Primary Completion Date :
Sep 1, 2011
Actual Study Completion Date :
Dec 1, 2011

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • Pegasys

    • Drug: ribavirin
    ribavirin 800 mg/day for 24 weeks
    Other Names:
  • 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 Names:
  • 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 Names:
  • Pegasys

    • Drug: Peginterferon alfa 2
    Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks
    Other Names:
  • Pegasys

    • Drug: ribavirin
    RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks
    Other Names:
  • 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 Names:
  • 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 Names:
  • Pegasys

    • Drug: ribavirin
    RBV 1600 mg/day 24 weeks
    Other Names:
  • peginterferon alfa 2 a
  • Epoetin beta

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment. [1 year]

    Secondary Outcome Measures

    1. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital Germans Trias i Pujol Badalona Barcelona Spain 08916
    2 Hospital de Bellvitge L´Hospitalet de Llobregat Barcelona Spain 08907
    3 Hospital Parc Taulí Sabadell Barcelona Spain 08208
    4 Hospital de Donostia San Sebastian Guipuzcoa Spain 20014
    5 Hospital Fundación Alcorcón Alcorcón Madrid Spain 28922
    6 Hospital de Getafe Getafe Madrid Spain 28901
    7 Hospital Puerta de Hierro Majadahonda Madrid Spain 28222
    8 Hospital Costa del Sol Marbella Málaga Spain 29603
    9 Hospital del Mar Barcelona Spain 08003
    10 Hospital Clinic i Provincial de Barcelona Barcelona Spain 08036
    11 Hospital Universitario Reina Sofía Córdoba Spain 14004
    12 Hospital Universitario Virgen de las Nieves Granada Spain 18004
    13 Hospital San Cecilio Granada Spain
    14 Hospital de León León Spain 24071
    15 Hospital La Princesa Madrid Spain 28006
    16 Hospital Gregorio Marañon Madrid Spain 28007
    17 Hospital 12 de Octubre Madrid Spain 28021
    18 Hospital Ramón y Cajal Madrid Spain 28034
    19 Hospital Clínico Universitario Virgen de la Victoria Málaga Spain 29010
    20 Hospital Central de Asturias Oviedo Spain 33006
    21 Hospital Clinico Universitario de Salamanca Salamanca Spain 37007
    22 Hospital Marqués de Valdecilla Santander Spain 39008
    23 Hospital de Valme Sevilla Spain 41014
    24 Hospital Clínico Universitario de Valencia Valencia Spain 46010
    25 Hospital Clínico Universitario de Valladolid Valladolid Spain 47005
    26 Hospital Santiago Apóstol Vitoria Spain 01004
    27 Hospital Clínico de Zaragoza Zaragoza Spain 50009
    28 Hospital Miguel Servet Zaragoza Spain 50009

    Sponsors and Collaborators

    • Dr. Conrado Fernandez

    Investigators

    • Study Director: Conrado M Fernandez-Rodriguez, Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Dr. Conrado Fernandez, MD, Hospital Universitario Fundación Alcorcón
    ClinicalTrials.gov Identifier:
    NCT00830609
    Other Study ID Numbers:
    • ROCHE FARMA S.A.
    First Posted:
    Jan 28, 2009
    Last Update Posted:
    Mar 13, 2012
    Last Verified:
    Mar 1, 2012
    Keywords provided by Dr. Conrado Fernandez, MD, Hospital Universitario Fundación Alcorcón
    Chronic Hepatitis C
    Genotype 3
    High viral load
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis C, Chronic
    Hepatitis
    Hepatitis, Chronic
    Ribavirin
    Peginterferon alfa-2a
    Interferon-alpha

    Study Results

    No Results Posted as of Mar 13, 2012