Clinical trial NCT00830609: High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis C
Keywords: Chronic Hepatitis C
Genotype 3
High viral load
Lead sponsor: Hospital Universitario Fundación Alcorcón
Sponsor class: OTHER
First posted: 2009-01-28
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of patients with RNA-HCV negative in each arm at week 24 after the end of treatment.
timeFrame: 1 year
Secondary outcomes:
measure: Rate of patients with undetectable RNA-HCV in each arm at week 4 and 24 of treatment. Rate of adverse effects in each arm.
timeFrame: 1 year
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: L´Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
state: Barcelona
city: San Sebastian
country: Spain
facility: Hospital de Donostia
state: Guipuzcoa
city: Alcorcón
country: Spain
facility: Hospital Fundación Alcorcón
state: Madrid
city: Getafe
country: Spain
facility: Hospital de Getafe
state: Madrid
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Granada
country: Spain
facility: Hospital San Cecilio
city: León
country: Spain
facility: Hospital de León
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Málaga
country: Spain
facility: Hospital Clínico Universitario Virgen de la Victoria
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital de Valme
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Vitoria
country: Spain
facility: Hospital Santiago Apóstol
city: Zaragoza
country: Spain
facility: Hospital Clínico de Zaragoza
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital Universitario Fundacion Alcorcon; University Rey Juan Carlos.
name: Conrado M Fernandez-Rodriguez
role: STUDY_DIRECTOR
References:
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.