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

This study has been completed.
Sponsor:
Collaborator:
Medecins Sans Frontieres
Information provided by (Responsible Party):
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00495326
First received: July 2, 2007
Last updated: February 14, 2012
Last verified: February 2012
History of Changes

July 2, 2007
February 14, 2012
December 2007
April 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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 ]
Complete list of historical versions of study NCT00495326 on ClinicalTrials.gov Archive Site
  • New or recurrent stage 3 or 4 HIV/AIDS related events [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Deaths after one year [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Severe drugs side effects [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Immune Reconstitution Syndrome(IRIS) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Increase of CD4 cell count induced by HAART [ Time Frame: at 6 months and 1 year ] [ Designated as safety issue: No ]
  • Pharmacokinetic profile of nevirapine when combined with rifampicin [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • Rifampicin plasma concentration dosage [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • New or recurrent stage 3 or 4 HIV/AIDS related events [ Time Frame: 12 months ]
  • Deaths after one year [ Time Frame: 12 months ]
  • Severe drugs side effects [ Time Frame: 12 months ]
  • Immune Reconstitution Syndrome(IRIS) [ Time Frame: 12 months ]
  • Increase of CD4 cell count induced by HAART [ Time Frame: at 6 months and 1 year ]
  • Pharmacokinetic profile of nevirapine when combined with rifampicin [ Time Frame: 2 months ]
Not Provided
Not Provided
 
Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146 CARINEMO)
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.

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.
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Tuberculosis
  • Aids
  • Hiv Infections
  • 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 Name: Triomune
  • 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
  • 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.
  • Experimental: 1
    Nevirapine-based ART
    Interventions:
    • Drug: Nevirapine based therapy
    • Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
  • Active Comparator: 2
    Efavirenz-based ART
    Interventions:
    • Drug: Efavirenz based therapy
    • Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
Bonnet M, Bhatt N, Baudin E, Silva C, Michon C, Taburet AM, Ciaffi L, Sobry A, Bastos R, Nunes E, Rouzioux C, Jani I, Calmy A; CARINEMO study group. Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial. Lancet Infect Dis. 2013 Apr;13(4):303-12. doi: 10.1016/S1473-3099(13)70007-0. Epub 2013 Feb 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
570
April 2011
April 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Mozambique
 
NCT00495326
ANRS 12146 CARINEMO
Yes
French National Agency for Research on AIDS and Viral Hepatitis
French National Agency for Research on AIDS and Viral Hepatitis
Medecins Sans Frontieres
Principal Investigator: Maryline Bonnet, MD Epicentre
Principal Investigator: Nilesh Bhatt, MD Ministry of Health, Instituto Nacional de Saude, Mozambique
French National Agency for Research on AIDS and Viral Hepatitis
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP