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

Primary Purpose

Chronic Hepatitis C

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Peginterferon alfa 2 A
Peginterferon alfa 2 A, ribavirin + Epo Beta
ribavirin
ribavirin
Peginterferon alfa 2
ribavirin
Sponsored by
Dr. Conrado Fernandez
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Chronic Hepatitis C, Genotype 3, High viral load

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Germans Trias i Pujol
  • Hospital de Bellvitge
  • Hospital Parc Taulí
  • Hospital de Donostia
  • Hospital Fundación Alcorcón
  • Hospital de Getafe
  • Hospital Puerta de Hierro
  • Hospital Costa del Sol
  • Hospital del Mar
  • Hospital Clinic i Provincial de Barcelona
  • Hospital Universitario Reina Sofía
  • Hospital Universitario Virgen de las Nieves
  • Hospital San Cecilio
  • Hospital de León
  • Hospital La Princesa
  • Hospital Gregorio Marañon
  • Hospital 12 de Octubre
  • Hospital Ramón y Cajal
  • Hospital Clínico Universitario Virgen de la Victoria
  • Hospital Central de Asturias
  • Hospital Clinico Universitario de Salamanca
  • Hospital Marqués de Valdecilla
  • Hospital de Valme
  • Hospital Clínico Universitario de Valencia
  • Hospital Clínico Universitario de Valladolid
  • Hospital Santiago Apóstol
  • Hospital Clínico de Zaragoza
  • Hospital Miguel Servet

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

A

B1

B2

Arm Description

Patients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks).

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.

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.

Outcomes

Primary Outcome Measures

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

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.

Full Information

First Posted
January 27, 2009
Last Updated
March 12, 2012
Sponsor
Dr. Conrado Fernandez
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1. Study Identification

Unique Protocol Identification Number
NCT00830609
Brief Title
High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3
Acronym
DARGEN-3
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 Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Conrado Fernandez

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
Chronic Hepatitis C, Genotype 3, High viral load

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
101 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
Patients in this arm will receive standard of care (Peginterferon alfa 2A 180 mcg/weeks SC plus ribavirin 800 mg/day for 24 weeks).
Arm Title
B1
Arm Type
Experimental
Arm Description
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.
Arm Title
B2
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Peginterferon alfa 2 A
Other Intervention Name(s)
Pegasys
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Peginterferon alfa 2 A, ribavirin + Epo Beta
Other Intervention Name(s)
Pegasys
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
ribavirin
Other Intervention Name(s)
peginterferon alfa 2 a, Epoetin beta
Intervention Description
RBV 1600 mg/day 24 weeks
Intervention Type
Drug
Intervention Name(s)
ribavirin
Other Intervention Name(s)
Pegasys
Intervention Description
ribavirin 800 mg/day for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Peginterferon alfa 2
Other Intervention Name(s)
Pegasys
Intervention Description
Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks
Intervention Type
Drug
Intervention Name(s)
ribavirin
Other Intervention Name(s)
Pegasys
Intervention Description
RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks
Primary Outcome Measure Information:
Title
Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Conrado M Fernandez-Rodriguez
Organizational Affiliation
Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital de Bellvitge
City
L´Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Parc Taulí
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital de Donostia
City
San Sebastian
State/Province
Guipuzcoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Fundación Alcorcón
City
Alcorcón
State/Province
Madrid
ZIP/Postal Code
28922
Country
Spain
Facility Name
Hospital de Getafe
City
Getafe
State/Province
Madrid
ZIP/Postal Code
28901
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Costa del Sol
City
Marbella
State/Province
Málaga
ZIP/Postal Code
29603
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Clinic i Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario Reina Sofía
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario Virgen de las Nieves
City
Granada
ZIP/Postal Code
18004
Country
Spain
Facility Name
Hospital San Cecilio
City
Granada
Country
Spain
Facility Name
Hospital de León
City
León
ZIP/Postal Code
24071
Country
Spain
Facility Name
Hospital La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
ZIP/Postal Code
28021
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Clínico Universitario Virgen de la Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Central de Asturias
City
Oviedo
ZIP/Postal Code
33006
Country
Spain
Facility Name
Hospital Clinico Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Marqués de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital de Valme
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Hospital Clínico Universitario de Valladolid
City
Valladolid
ZIP/Postal Code
47005
Country
Spain
Facility Name
Hospital Santiago Apóstol
City
Vitoria
ZIP/Postal Code
01004
Country
Spain
Facility Name
Hospital Clínico de Zaragoza
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Hospital Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
24360571
Citation
Fernandez-Rodriguez CM, Morillas RM, Masnou H, Navarro JM, Barcena R, Gonzalez JM, Martin-Martin L, Poyato A, Miquel-Planas M, Jorquera F, Casanovas T, Salmeron J, Calleja JL, Sola R, Alonso S, Planas R, Romero-Gomez M. Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study. Gastroenterol Hepatol. 2014 Jan;37(1):1-8. doi: 10.1016/j.gastrohep.2013.10.005. Epub 2013 Dec 17.
Results Reference
derived

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

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