Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients (LIVERAL)

April 1, 2026 updated by: ANRS, Emerging Infectious Diseases

A Pilot Study of Pharmacokinetics, Tolerance and Efficacy of Raltegravir Combined to Two Fully Active Molecules Among Nucleosi(ti)de Analogs and Enfuvirtide Before and After Liver Transplant in HIV Infected Patients With End Stage Liver Disease (ANRS 148 LIVERAL)

This phase I/II, multi-center study is designed to determine the pharmacokinetic profile of Raltegravir in patients with end stage liver disease and to assess drug-drug interaction when Raltegravir is combined with immunosuppressive therapy in liver transplant recipients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

HIV infected patients with stable plasma HIV-RNA below 50 copies per mL and severe liver dysfunction will be switched from their antiretroviral regimen to a combination of raltegravir (one 400 mg pill twice daily) and two fully active molecules among nucleosi(ti)de analogs and enfuvirtide for a first period of at least 3 months and a second period of at least 3 months after liver transplantation, if need be, when a steady state of the anticalcineurin will be reached. Pharmacokinetic parameters of raltegravir will be calculated during severe liver dysfunction period and after liver transplantation. Pharmacokinetic parameters of cyclosporine (or tacrolimus if contra indication to cyclosporine) will be compared when administrated alone or combined with raltegravir. Patients will be followed up according to standard of care. This study will be divided in two distinct periods (1 and 2) lasting 3 months each. Period 1 will start from the inclusion in the study and will generally include the switch to raltegravir. Period 2 will start from liver transplantation.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Le Kremlin-Bicêtre, France, 94275
        • Service de Médecine Interne, Hôpital de Bicêtre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18
  • Documented HIV-1 infection, hepatitis B or C co-infection is allowed
  • Plasma viral load at screening visit below 50 copies per mL for at least 6 months
  • Patient with severe liver failure (Meld Score ≥ 15 and/or refractory ascites and/or haemorrhage of digestive tract and/or hepatic encephalopathy) for taking part into period 1
  • Patient eligible for the liver transplant waiting list or immediate post transplantation for taking part into period 2
  • Abstinence from alcohol intake for at least 6 months (WHO norm)
  • Withdrawal from intravenous drug use for at least 6 months (methadone substitution is permitted)
  • No ongoing class C opportunistic infection (1993 CDC classification)
  • Patient whose clinical and immunovirological condition allows triple therapy with raltegravir + 2 NRTI or raltegravir + NRTI + enfuvirtide

  • Patient whose HIV population, according to cumulative genotypes carried out on viral RNA together with treatment history (if available and interpreted as per the ANRS-AC11 algorithm version no.19) does not present a profile of mutations associated with resistance to raltegravir and is sensitive to at least two fully active* agents selected among nucleoside/nucleotide reverse transcriptase analogs NRTI (abacavir, lamivudine, emtricitabine, tenofovir) or enfuvirtide

    *An ARV agent is considered to be fully active if the cumulative genotypes do not show any mutation associated with resistance or any mutation associated with "possible resistance"

  • Patient not having experienced viral escape during treatment combining 3TC, FTC or raltegravir
  • Patient registered with or covered by a social security scheme
  • For women of child-bearing potential, use of a barrier contraceptive method during sexual intercourse and negative pregnancy test (plasma ß-HCG ) at screening visit
  • Informed consent form signed at screening visit at the latest

Exclusion Criteria:

  • More than two virological failures during antiretroviral treatment
  • Currently receiving treatment with an agent in development (apart from an authorization for temporary use)
  • Plasma viral load at screening visit ≥ 50 copies per mL during at least the last 6 months
  • Pregnant women, or women liable to become pregnant, breast-feeding women, no contraception, or refusal to use contraception
  • All conditions (including but not limited to alcohol intake and drug use) liable to compromise, in the investigator's opinion, the safety of treatment and/or the patient's compliance with the protocol
  • Patient not having any effective options for NRTI +/- enfuvirtide (defined in the inclusion criteria)
  • Ongoing treatment with interferon-alpha or ribavirin for hepatitis C

  • Concomitant medication including one or more agents liable to induce UGT1A1 and reduce raltegravir concentrations:

    • anti-infective agents: rifampicin/rifampin
    • psychotropic/antiepileptic agents: phenytoin, phenobarbital, carbamazepine
    • steroidal anti-inflammatory drug: dexamethasone

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Raltegravir potassium
raltegravir 400 mg twice a day
Drug: Raltegravir potassium
one pill of raltegravir 400 mg twice a day
Other Names:
  • ISENTRESS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic parameters of raltegravir in patients with severe liver dysfunction and after a liver transplantation when combined to immunosuppressive therapy. Pharmacokinetic parameters of immunosuppressive drugs with or without raltegravir
Time Frame: at month 1 for period 1 and day 7-month 1 for period 2
at month 1 for period 1 and day 7-month 1 for period 2

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the maintenance of the virological efficacy on HIV of raltegravir combined with two fully active molecules among NRTI (or NRTI + enfuvirtide). Follow-up over a 3-months period before and after transplantation
Time Frame: from day 0 to month 3 for period 1 and period 2
from day 0 to month 3 for period 1 and period 2
To assess the safety of raltegravir before transplantation in patients with impaired liver function, and after transplantation in combination with immunosuppressive treatment
Time Frame: from day 0 to month 3 for period 1 and period 2
from day 0 to month 3 for period 1 and period 2
To describe the clinical outcome of patients (such as the onset of opportunistic infections, relapse of HCV infection, morphological and metabolic disorders outcomes)
Time Frame: from day 0 to month 3 for period 1 and period 2
from day 0 to month 3 for period 1 and period 2
To describe the changes in liver function (evaluation of liver function during treatment) before and after liver transplantation
Time Frame: from day 0 to month 3 for period 1 and period 2
from day 0 to month 3 for period 1 and period 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Elina TEICHER, MD, Hôpital de Bicêtre - LE KREMLIN-BICETRE - FRANCE
  • Study Chair: Jean-Pierre ABOULKER, MD, INSERM SC10 Villejuif France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

November 26, 2009

First Submitted That Met QC Criteria

November 30, 2009

First Posted (Estimated)

December 1, 2009

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

April 1, 2026

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 148 LIVERAL (ANRS)
  • 2009-014616-36 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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