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TuberculosisPhase 2/3CARINEMONCT00495326

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

A Phase 2/3 study testing Nevirapine based therapy, Efavirenz based therapy and Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) in people with Tuberculosis and Aids, run by French National Agency for Research on AIDS and Viral Hepatitis at 3 sites in Mozambique.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tuberculosis, Aids, Hiv Infections
What is being tested?
Nevirapine based therapy, Efavirenz based therapy and Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
570 participants
Where
3 sitesMozambique
Study dates
Dec 2007to Apr 2011
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country.

Mozambique3 sites

  • Health centre of Alto Mae, Chamanculo district

    Maputo

  • Health centre of Josue Macao

    Maputo

  • Health centre of Malavane

    Maputo

Other trials in Mozambique

About this study

Official title: 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.

Read the 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.

Being tested
Nevirapine based therapy, Efavirenz based therapy, Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
Keywords
drug interactions, Treatment Naive
Medical subject headings
Tuberculosis, Acquired Immunodeficiency Syndrome, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nevirapine based therapyDrug

    Also called Triomune

    • 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)

  • Efavirenz based therapyDrug

    Also called Stockrin, Cipla drugs

    Efavirenz EFV 200 mg (3 tablets/d) Lamivudine 3TC 300mg (2 tablets of 150mg/d) D4T generic 30mg or 40mg (2 tablets/d)

  • Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)Drug

    • 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.
Study groups in NCT00495326
Study groupRoleWhat they receive
1ExperimentalNevirapine-based ART
Receives: Drug: Nevirapine based therapy; Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
2Active comparatorEfavirenz-based ART
Receives: Drug: Efavirenz based therapy; Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.)

    Measured: 3, 6 and 12 months

Secondary outcomes (7)

  1. New or recurrent stage 3 or 4 HIV/AIDS related events

    Measured: 12 months

  2. Deaths after one year

    Measured: 12 months

  3. Severe drugs side effects

    Measured: 12 months

  4. Immune Reconstitution Syndrome(IRIS)

    Measured: 12 months

  5. Increase of CD4 cell count induced by HAART

    Measured: at 6 months and 1 year

  6. Pharmacokinetic profile of nevirapine when combined with rifampicin

    Measured: 2 months

  7. Rifampicin plasma concentration dosage

    Measured: 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2007 (estimated)
  2. Study startDec 2007
  3. Primary completionApr 2011
  4. Study completionApr 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
570 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00495326
Sponsor's protocol ID
ANRS 12146 CARINEMO
Acronym
CARINEMO
Status last verified
Feb 2012
First submitted
2 Jul 2007
Last updated
15 Feb 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Bhatt NB, Barau C, Amin A, Baudin E, Meggi B, Silva C, Furlan V, Grinsztejn B, Barrail-Tran A, Bonnet M, Taburet AM; ANRS 12146-CARINEMO Study Group. Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment. Antimicrob Agents Chemother. 2014 Jun;58(6):3182-90. doi: 10.1128/AAC.02379-13. Epub 2014 Mar 24.

    PubMed 24663014

  • 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.

    PubMed 23433590

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Nevirapine based therapy, Efavirenz based therapy and Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) in people with Tuberculosis and Aids, run by French National Agency for Research on AIDS and Viral Hepatitis at 3 sites in Mozambique.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Mozambique. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00495326, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2012.

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