Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146 CARINEMO) (CARINEMO)

February 14, 2012 updated by: French National Agency for Research on AIDS and Viral Hepatitis

Randomized Non-inferiority Trial Comparing the Nevirapine-based Antiretroviral Therapy Versus the Standard Efavirenz-based ART for the Treatment of HIV-TB Co-infected Patients on Rifampicin-based Therapy (ANRS 12146 CARINEMO)

The purpose of this study is to determine whether the use of Nevirapine in HIV patients already treated against tuberculosis by Rifampicin is as efficient and as well tolerated as Efavirenz.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Anti Retroviral Therapy (ART) reduces tuberculosis (TB) incidence in HIV-infected patients and reduces mortality among TB patients with deep immune suppression. The Fixed Drug Combination (FDC) nevirapine (NVP)-lamivudine-stavudine is the first line ART available for low-income countries. Rifampicin (RMP), due to its liver induction effect, reduces significantly NVP plasma concentration, raising concerns regarding the risk of resistance and subsequent treatment failure. Therefore, in co-infected patients, WHO recommends delaying ART or using efavirenz (EFV)-based ART. Although EFV is also reduced at lower level, longitudinal studies report good efficacy and safety when given concomitantly with RMP.

In low-income countries, poor access to EFV, contradiction during pregnancy and absence of FDC containing EFV lead to difficulties in HIV-TB treatment.

Despite 2 limited retrospective studies and a non-randomised prospective study, which report good virological response at 6 months in co-infected patients receiving NVP and RMP co-administration, existing data are too limited to change the recommendation.

The aim of the study is to compare, in terms of therapeutic efficacy and clinical safety, the nevirapine-based HAART to the standard efavirenz-based HAART, in HIV/TB co-infected patients receiving a rifampicin-based TB treatment.

The study will evaluate one year after TB treatment initiation, whether the HAART efficacy (virological outcome, death or lost of follow-up) induced by NVP-based HAART is non-inferior to those induced by EFV based HAART, in patients receiving concomitantly HAART and RMP-based TB treatment.

Study Type

Interventional

Enrollment (Actual)

570

Phase

  • Phase 2
  • Phase 3

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

  • Mozambique
      • Maputo, Mozambique
        • Health centre of Alto Mae, Chamanculo district
      • Maputo, Mozambique
        • Health centre of Josue Macao
      • Maputo, Mozambique
        • Health centre of Malavane

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Person HIV infected
  • Aged of 18 years or more
  • Signed informed consent
  • New case of tuberculosis: patient who never received TB treatment or for less than 1 month
  • Patients receiving rifampicin based TB regimen since 4 to 6 weeks
  • CD4 cell count < 250 cell/mm3 in the 4 weeks following the TB diagnosis
  • Naïve of HAART
  • For women of childbearing age, to have a negative plasmatic test for pregnancy and to accept to take a contraception or declare no wish of pregnancy in the coming year.

Exclusion Criteria:

  • To have a positive plasmatic test for pregnancy
  • Karnofsky score <60%
  • ALAT > 4N (Hepatitis grade 3 or 4)
  • Ongoing psychiatric pathology
  • Refuse to participate in the study

Amendment :

  • bilirubin > grade 3
  • any grade 4 clinical sign or biological result at time of inclusion

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Nevirapine-based ART
Drug: Nevirapine based therapy
  • Patients below 60 kg: 1 tablet twice a day of Triomune30®, including NVP 200 mg, 3TC 150 mg and D4T 30mg
  • Patients above 60kg: 1 tablet twice a day of Triomune40®, including NVP 200 mg, 3TC 150 mg and D4T 40 mg)
Other Names:
  • Triomune
Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
  • Intensive phase: 2 months daily E(RMP)HZ. PTB smear positive patients at month 2 will receive 1 more month intensive phase.
  • Continuation phase: 4 months daily H(RMP).
  • Patients with meningitis will receive Streptomycin instead of E during intensive phase.
Active Comparator: 2
Efavirenz-based ART
Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
  • Intensive phase: 2 months daily E(RMP)HZ. PTB smear positive patients at month 2 will receive 1 more month intensive phase.
  • Continuation phase: 4 months daily H(RMP).
  • Patients with meningitis will receive Streptomycin instead of E during intensive phase.
Drug: Efavirenz based therapy
Efavirenz EFV 200 mg (3 tablets/d) Lamivudine 3TC 300mg (2 tablets of 150mg/d) D4T generic 30mg or 40mg (2 tablets/d)
Other Names:
  • Stockrin
  • Cipla drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Viral load measure (Virological failure will be defined after 2 consecutive measures as : More than 1 log10 increase in plasma HIV-1 RNA concentration for patients with detectable viral load (> 50 copies/mL) at the previous dosage.)
Time Frame: 3, 6 and 12 months
3, 6 and 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
New or recurrent stage 3 or 4 HIV/AIDS related events
Time Frame: 12 months
12 months
Deaths after one year
Time Frame: 12 months
12 months
Severe drugs side effects
Time Frame: 12 months
12 months
Immune Reconstitution Syndrome(IRIS)
Time Frame: 12 months
12 months
Increase of CD4 cell count induced by HAART
Time Frame: at 6 months and 1 year
at 6 months and 1 year
Pharmacokinetic profile of nevirapine when combined with rifampicin
Time Frame: 2 months
2 months
Rifampicin plasma concentration dosage
Time Frame: 2 months
2 months

Collaborators and Investigators

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

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis

Collaborators

Medecins Sans Frontieres, Netherlands

Investigators

  • Principal Investigator: Maryline Bonnet, MD, Epicentre
  • Principal Investigator: Nilesh Bhatt, MD, Ministry of Health, Instituto Nacional de Saude, Mozambique

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.

General Publications

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

December 1, 2007

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

July 2, 2007

First Submitted That Met QC Criteria

July 2, 2007

First Posted (Estimate)

July 3, 2007

Study Record Updates

Last Update Posted (Estimate)

February 15, 2012

Last Update Submitted That Met QC Criteria

February 14, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 12146 CARINEMO

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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