Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the "The HEPAVIR HEPATIC SAFETY Cohort." (hEPAtic)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:
NCT02196064
First received: July 15, 2014
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

To evaluate the incidence of grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects.


Condition
Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the "The HEPAVIR HEPATIC SAFETY Cohort." hEPAtic Study.

Resource links provided by NLM:


Further study details as provided by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud:

Primary Outcome Measures:
  • Incidence of hepatic events [ Time Frame: First 48 weeks of antiretroviral therapy ] [ Designated as safety issue: Yes ]
    Number of patients with grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects.


Secondary Outcome Measures:
  • Comparison of hepatic events between exposed and unexposed to Eviplera® [ Time Frame: First 48 weeks of antiretroviral therapy ] [ Designated as safety issue: Yes ]

    We evaluated the following parameters between subjets exposed and unexposed to Eviplera®

    • Incidence of hepatic toxicity
    • Incidence of hepatic adverse events.
    • Proportion of subjects who interrupt treatment due to liver toxicity according to Eviplera® exposure

    We will evaluated this parameters taking account the impact of baseline liver fibrosis/cirrhosis on liver toxicity.


  • Viral Kinetics and Immune response [ Time Frame: 48 weeks of antiretroviral therapy ] [ Designated as safety issue: No ]

    Viral kinetics.- We compare the viral load between patients exposed and not exposed with Eviplera.

    Immune response.- We compare number of CD4 cells between patients exposed and not exposed with Eviplera



Estimated Enrollment: 528
Study Start Date: May 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Safety of the three-drug combination TDF/FTC/RPV
A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group.

Detailed Description:

This is a retrospective analysis of the prospective multicenter, observational "HEPAVIR HEPATIC SAFETY Cohort" (NCT01908660), in which the hepatic safety of the three-drug combination TDF/FTC/RPV will be assessed. A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group.

The main objective is to evaluate the incidence of grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects.

Variables collected within in the cohort:

  • Demographic variable: age, sex.
  • Variables related to hepatitis C virus-infection: infection route, genotype, grade of hepatic fibrosis and method used for its determination, baseline Child-Pugh index in patients with cirrhosis, previous hepatic decompensations.
  • Variables related to HIV-infection: CDC clinical category, HIV viral load, CD4 cell count, previous and new antiretroviral drugs.
  • Blood test: AST, ALT platelets, cholesterol, bilirubin, gamma-glutamyltransferase, alkaline phosphatase, creatinine.
  • Other variables: alcohol intake, self-reported adverse events, abnormal clinical findings.
  • Cause of discontinuing antiviral when applicable.

Endpoints

  1. Primary endpoint: Emergence of grade 3-4 TEs/grade 4 TBEs (hepatic toxicity) from baseline to week 48.
  2. Secondary endpoints

    • Emergence of hepatic adverse events.
    • Drug interruptions due to liver toxicity.
    • Development of hepatic decompensations.
    • CD4 and viral load changes from baseline to week 48.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group.

Criteria

Inclusion Criteria:

  • ≥ 18 years old.
  • Chronic HIV-1 infection, as diagnosed on the basis of the presence of serum HIV antibodies detected by EIA and western-blot.
  • Chronic HCV infection as proven by detecting HCV antibodies in plasma, as well as detectable plasma HCV-RNA by PCR.
  • To start a new ART regimen during the study period.

Exclusion Criteria:

  • Subjects with hepatotoxic events in the 2 months previous to Eviplera® treatment.
  • Acute infections or uncontrolled chronic infection in the two months previous to Eviplera® treatment.
  • Concomitant use of any drug with potential drug-drug interaction with Eviplera®.
  • Documented resistance to study drugs.
  • Concomitant therapy including anti-HCV agents, cytotoxic chemotherapy or immunosuppressors during Eviplera® treatment.
  • Subjects taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks before Eviplera® treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02196064

Contacts
Contact: Juan Antonio Pineda Vergara japineda@telefonica.net

Locations
Spain
Fundación Pública Andaluza Progreso y Salud Recruiting
Sevilla, Spain, 41092
Contact: Marta Reboredo Ares       gestionensayosclinicos.fps@juntadeandalucia.es   
Sponsors and Collaborators
Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
Gilead Sciences
Investigators
Study Chair: Juan Antonio Pineda Vergara Hospital Universitario Virgen de Valme
Study Chair: Antonio Rivero Román Hospital Universitario Reina Sofía
Principal Investigator: Dolores Merino Muñoz Complejo Hospitalario de Especialidades Juan Ramón Jimenez
Principal Investigator: María José Rios Villega Hospital Universitario Virgen Macarena
Principal Investigator: Francisco Téllez Pérez Hospital La Línea de la Concepción
Principal Investigator: Inés Pérez Camacho Hospital de Poniente
Principal Investigator: Antonio Collado Romacho Complejo Hospitario Torrecárdenas
Principal Investigator: Josefa Ruiz Morales Hospital Universitario Virgen de la Victoria
Principal Investigator: Marcial Delgado Fernández Hospital Regional Universitario de Málaga
Principal Investigator: Leopoldo Muñoz Medina Hospital Universitario San Cecilio
Principal Investigator: Francisco Vera Méndez Hospital Santa María de Rosell
Principal Investigator: Nuria Espinosa Aguilera Hospitales Universitarios Virgen del Rocío
Principal Investigator: Iganacio Santos Gil Hospital Universitario de la Princesa
Principal Investigator: Juan González García Hospital Universitario La Paz
Principal Investigator: Antonio Vergara de Campos Hospital Universitario de Puerto Real
Principal Investigator: Juan Berenguer Berenguer Hospital Universitario Gregorio Marañón
Principal Investigator: Federico Pulido Ortega Hospital 12 de Octubre
  More Information

No publications provided

Responsible Party: Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT02196064     History of Changes
Other Study ID Numbers: hEPAtic
Study First Received: July 15, 2014
Last Updated: July 17, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud:
HIV HCV antiretroviral

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis A
Hepatitis C
Immunologic Deficiency Syndromes
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Lentivirus Infections
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014