Clinical trial NCT00526448: Phase IV Study to Evaluate the Efficacy/Safety to Extend Treatment and High Dose of Ribavirin in co-Infected Patients
Official title: Open, Multicentre,Randomized Phase IV Trial to Evaluate Efficacy/Safety to Extend Treatment Duration With Peginterferon Alfa-2a+High Dose of Ribavirin Supporting Epo β in Treatment of CHC in HIV-HCV Patients Who Not Clear Virus at Week 4
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis C
Keywords: high dose of ribavirin
extend treatment duration
tailoring treatment
Lead sponsor: Hospital Carlos III, Madrid
Sponsor class: OTHER
First posted: 2007-09-10
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: % patients with RNA-HCV < 50 UI/ml
timeFrame: 24 weeks after the end of treatment
Secondary outcomes:
measure: % patients with RNA-HCV < 50 UI/ml
timeFrame: 4 weeks on treatment
Other outcomes:
Locations:
city: Vitoria
country: Spain
facility: Hospital Txagorritxu
state: Alava
city: Elche
country: Spain
facility: Hospital General de Elche
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Son Dureta
state: Baleares
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
state: Barcelona
city: Jerez de la Frontera
country: Spain
facility: Hospital General de Jerez de la Frontera
state: Cadiz
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
state: Cantabria
city: Puerto del Rosario
country: Spain
facility: Hospital General de Fuerteventura
state: Fuerteventura
city: Las Palmas de Gran Canarias
country: Spain
facility: Hospital Doctor Negrín
state: Gran Canaria
city: Ferrol
country: Spain
facility: Hospital Arquitecto Marcide
state: La Coruña
city: Santiago
country: Spain
facility: Hospital Clínico Universitario
state: La Coruña
city: Alcorcon
country: Spain
facility: Hospital de Alcorcon
state: Madrid
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
state: Madrid
city: Vigo
country: Spain
facility: Hospital Xeral-Cíes
state: Pontevedra
city: Vigo
country: Spain
facility: Hospital do Meixoeiro
state: Pontevedra
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Santa Cruz de Tenerife
city: La Palma
country: Spain
facility: Hospital General de la Palma
state: Santa Cruz de Tenerife
city: Baracaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: A Coruña
country: Spain
facility: Hospital Juan Canalejo
city: Albacete
country: Spain
facility: Hospital de Albacete
city: Barcelona
country: Spain
facility: Hospital Santa Creu y Sant Pau
city: Granada
country: Spain
facility: Hospital Clínico san Cecilio
city: Huesca
country: Spain
facility: Hospital San Jorge
city: Lugo
country: Spain
facility: Hospital Xeral-Caldé
city: Madrid
country: Spain
facility: Hospital de la Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Carlos III
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Murcia
country: Spain
facility: Hospital Santa Maria del Rosell
city: Málaga
country: Spain
facility: Hospital Clínico Virgen de la Victoria
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital de la Candelaria
city: Sevilla
country: Spain
facility: Hospital Virgen de la Macarena
city: Sevilla
country: Spain
facility: Hospital de Valme
city: Valencia
country: Spain
facility: Hospital Universitario la Fé
city: Valencia
country: Spain
facility: Hospial Clinico Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Clínico de Valladolid
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital Carlos III. Madrid. Spain
name: Vicente Soriano, Dr
role: STUDY_CHAIR
References:
citation: Vispo E, Labarga P, Guardiola JM, Barreiro P, Miralles C, Rubio R, Miralles P, Aguirrebengoa K, Portu J, Morello J, Rodriguez-Novoa S, Soriano V; PERICO Study Group. Preemptive erythropoietin plus high ribavirin doses to increase rapid virological responses in HIV patients treated for chronic hepatitis C. AIDS Res Hum Retroviruses. 2010 Apr;26(4):419-24. doi: 10.1089/aid.2009.0120.