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

Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects Clinical Trial

— hEPAtic  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02196064
• Other study ID #: hEPAtic
• Status: Completed
• Phase: N/A
• First received: July 15, 2014
• Last updated: August 4, 2015
• Start date: May 2014
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 519
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Hepatitis
• Hepatitis A
• Hepatitis C
• HIV Infections
• Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects
• Immunologic Deficiency Syndromes

Locations

Country	Name	City	State
Spain	Fundación Pública Andaluza Progreso y Salud	Sevilla

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Pública Andaluza Progreso y Salud	Gilead Sciences

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of hepatic events	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.	First 48 weeks of antiretroviral therapy	Yes
Secondary	Comparison of hepatic events between exposed and unexposed to Eviplera®	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.	First 48 weeks of antiretroviral therapy	Yes
Secondary	Viral Kinetics and Immune response	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	48 weeks of antiretroviral therapy	No