Phase IV Study to Evaluate the Efficacy/Safety to Extend Treatment and High Dose of Ribavirin in co-Infected Patients
- Conditions
- Chronic Hepatitis C
- Interventions
- Registration Number
- NCT00526448
- Lead Sponsor
- Hospital Carlos III, Madrid
- Brief Summary
To compare the sustained virological response (SVR = ribonucleic acid (RNA) - hepatitis C virus (HCV) undetectable at week 24 before end the treatment) in chronic hepatitis C patients genotype 1-4 co-infected with HIV-HCV, treated with Peginterferón alfa-2a (40 KD) 180 µg/week and Ribavirin (2000 mg/day during 4 weeks, follow of 1000-1200 mg/day, according to body weight); versus Peginterferón alfa-2a (40 KD) 180 μg/week and Ribavirin (1000-1200 mg/day, according to body weight).
To evaluate the impact to extend the treatment with Peginterferon alfa-2a and Ribavirin to week 72, in SVR of these patients with genotypes 1-4 without rapid virological response (RVR = RNA - HCV undetectable at 4 week).
- Detailed Description
The PRESCO study (ribavirin dose 1000-1200 mg/day) emphasized that optimal ribavirin exposure seems to be crucial to maximize sustained virological response and minimize the incidence of relapses after treatment discontinuations.
Recent reports showed that it is beneficial to extend the treatment duration in patients without rapid virological response at 4 weeks (RNA-HCV \< 50 UI/ml).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 384
- Male and female patients > 18 years of age
- Serologic evidence of anti-HCV
- Detectable plasma HCV-RNA
- Serologic evidence of HIV-1 infection
- CD4 cell count >/= 250 cell/mm3
- Stable status of HIV-1 infection in the opinion of the investigator
- Patients on stable antiretroviral therapy (HAART) for at least 6 weeks prior to baseline whose HAART regimen (drugs and dosage) is expected to remain unaltered for the first 6 weeks of this study
- Patients who have not been on HAART for at least 6 weeks prior to randomization who are willing to delay initiation of HAART therapy for at least 6 weeks
- Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
- Willingness to give written informed consent
- Women with ongoing pregnancy or breast feeding
- Male partners of women who are pregnant
- IFN/ribavirin therapy at any previous time
- Child Pugh > 6 (Child Pugh B or C)
- History or conditions consistent with decompensated liver disease
- Any investigational drug 6 weeks prior to the first dose of study drug (expanded access programs for HIV treatment are allowed)
- Patients treated with didanosine and/or zidovudine
- Positive test at anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBeAg
- History or other evidence of a medical condition associated with chronic liver disease other than HCV
- Hepatocarcinoma observed in the liver ecography
- Serum concentrations of ceruloplasmin or alfa1-antitrypsin at screening consistent with an increased risk of metabolic liver disease
- Active HIV-related opportunistic infection and/or malignancy requiring acute systemic therapy
- Absolute neutrophil count (ANC) < 1500 cells/mm3
- Hgb < 11 g/dL in women or 12 g/dL in men or any patient for whom anemia would be medically problematic
- Hemoglobinopathy or any other cause of or tendency for hemolysis
- Platelet count < 50,000 cells/mm3
- History of G-CSF, GM-CSF or epo treatment during 3 months prior to the first dose of study drug
- Serum creatinine level > 1.5 times the upper limit of normal at screening
- History of severe psychiatric disease, especially depression
- History of a severe seizure disorder or current anticonvulsant use
- History of immunologically mediated disease
- History or other evidence of chronic pulmonary disease associated with functional limitation
- History of significant cardiac disease that could be worsened by acute anemia
- History of thyroid disease poorly controlled on prescribed medications
- Evidence of severe retinopathy
- History of major organ transplantation with an existing functional graft
- History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
- History of any systemic anti-neoplastic or immunomodulatory treatment 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
- Concomitant medication with rifampin/rifampicin, rifabutin, pyrazinamide, isoniazid, gancyclovir, thalidomide, oxymetholone, immunomodulatory treatments and systemic antiviral agents as adjuvant therapy for CHC
- Drug use within 6 months of 1st dose and excessive alcohol consumption
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 epoetin beta Peginterferon alfa-2a 180 mcg/week + ribavirin 2000 mg/day + epoetin beta 450 UI/week 2 ribavirin Peginterferon alfa-2a 180 mcg/week + ribavirin 1000-1200 mg/day 1 ribavirin Peginterferon alfa-2a 180 mcg/week + ribavirin 2000 mg/day + epoetin beta 450 UI/week 1 Peginterferon alfa-2a Peginterferon alfa-2a 180 mcg/week + ribavirin 2000 mg/day + epoetin beta 450 UI/week 2 Peginterferon alfa-2a Peginterferon alfa-2a 180 mcg/week + ribavirin 1000-1200 mg/day
- Primary Outcome Measures
Name Time Method % patients with RNA-HCV < 50 UI/ml 24 weeks after the end of treatment
- Secondary Outcome Measures
Name Time Method % patients with RNA-HCV < 50 UI/ml 4 weeks on treatment
Trial Locations
- Locations (40)
Hospital Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Hospital do Meixoeiro
🇪🇸Vigo, Pontevedra, Spain
Hospital Universitario de Canarias
🇪🇸La Laguna, Santa Cruz de Tenerife, Spain
Hospital General de la Palma
🇪🇸La Palma, Santa Cruz de Tenerife, Spain
Hospital Juan Canalejo
🇪🇸A Coruña, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Hospital Severo Ochoa
🇪🇸Leganés, Madrid, Spain
Hospital de Cruces
🇪🇸Baracaldo, Vizcaya, Spain
Hospital Santa Creu y Sant Pau
🇪🇸Barcelona, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital de Albacete
🇪🇸Albacete, Spain
Hospital San Jorge
🇪🇸Huesca, Spain
Hospital General de Jerez de la Frontera
🇪🇸Jerez de la Frontera, Cadiz, Spain
Hospital Clínico de Valladolid
🇪🇸Valladolid, Spain
Hospital Universitario la Fé
🇪🇸Valencia, Spain
Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Clínico de Salamanca
🇪🇸Salamanca, Spain
Hospital de la Princesa
🇪🇸Madrid, Spain
Hospital Santa Maria del Rosell
🇪🇸Murcia, Spain
Hospital Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Virgen de la Macarena
🇪🇸Sevilla, Spain
Hospital Xeral-Caldé
🇪🇸Lugo, Spain
Hospital Clínico Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital de Valme
🇪🇸Sevilla, Spain
Hospital General de Elche
🇪🇸Elche, Alicante, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital Txagorritxu
🇪🇸Vitoria, Alava, Spain
Hospital Son Dureta
🇪🇸Palma de Mallorca, Baleares, Spain
Hospital Doctor Negrín
🇪🇸Las Palmas de Gran Canarias, Gran Canaria, Spain
Hospital Clínico Universitario
🇪🇸Santiago, La Coruña, Spain
Hospital General de Fuerteventura
🇪🇸Puerto del Rosario, Fuerteventura, Spain
Hospital Arquitecto Marcide
🇪🇸Ferrol, La Coruña, Spain
Hospital de Alcorcon
🇪🇸Alcorcon, Madrid, Spain
Hospital Clínico san Cecilio
🇪🇸Granada, Spain
Hospital Clínico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Hospital Xeral-Cíes
🇪🇸Vigo, Pontevedra, Spain
Hospital de la Candelaria
🇪🇸Santa Cruz de Tenerife, Spain
Hospital Carlos III
🇪🇸Madrid, Spain
Hospial Clinico Universitario de Valencia
🇪🇸Valencia, Spain