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
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Aids
Hiv Infections
Drug: Nevirapine based therapy
Drug: Efavirenz based therapy
Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 570
Study Start Date: December 2007
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00495326

Locations
Mozambique
Health centre of Alto Mae, Chamanculo district
Maputo, Mozambique
Health centre of Josue Macao
Maputo, Mozambique
Health centre of Malavane
Maputo, Mozambique
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Medecins Sans Frontieres
Investigators
Principal Investigator: Maryline Bonnet, MD Epicentre
Principal Investigator: Nilesh Bhatt, MD Ministry of Health, Instituto Nacional de Saude, Mozambique
  More Information

Additional Information:
No publications provided by French National Agency for Research on AIDS and Viral Hepatitis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier: NCT00495326     History of Changes
Other Study ID Numbers: ANRS 12146 CARINEMO
Study First Received: July 2, 2007
Last Updated: February 14, 2012
Health Authority: Mozambique: Ministry of Health (MISAU)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
drug interactions
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mycobacterium Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Nevirapine
Rifampin
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antibiotics, Antitubercular
Antitubercular Agents
Antiviral Agents
Enzyme Inhibitors
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014