Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146 CARINEMO)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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) |
- 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 ]
- 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
Other Name: Triomune
Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
|
|
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:
Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
|
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 |
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| Mozambique | |
| Health centre of Alto Mae, Chamanculo district | |
| Maputo, Mozambique | |
| Health centre of Josue Macao | |
| Maputo, Mozambique | |
| Health centre of Malavane | |
| Maputo, Mozambique | |
| 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:
|
HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections |
Bacterial Infections Ethambutol Isoniazid Rifampin Efavirenz Nevirapine Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Fatty Acid Synthesis Inhibitors Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013