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

Hiv Infections Clinical Trial

— CARINEMO  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00495326
• Other study ID #: ANRS 12146 CARINEMO
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 2, 2007
• Last updated: February 14, 2012
• Start date: December 2007
• Est. completion date: April 2011

Study information

• Verified date: February 2012
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mozambique: Ministry of Health (MISAU)
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 570
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aids
• Hiv Infections
• Tuberculosis

Intervention

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)
• 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)
• 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.

Locations

Country	Name	City	State
Mozambique	Health centre of Alto Mae, Chamanculo district	Maputo
Mozambique	Health centre of Josue Macao	Maputo
Mozambique	Health centre of Malavane	Maputo

Sponsors (2)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Medecins Sans Frontieres

Country where clinical trial is conducted

Mozambique, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.)		3, 6 and 12 months	No
Secondary	New or recurrent stage 3 or 4 HIV/AIDS related events		12 months	No
Secondary	Deaths after one year		12 months	Yes
Secondary	Severe drugs side effects		12 months	Yes
Secondary	Immune Reconstitution Syndrome(IRIS)		12 months	Yes
Secondary	Increase of CD4 cell count induced by HAART		at 6 months and 1 year	No
Secondary	Pharmacokinetic profile of nevirapine when combined with rifampicin		2 months	Yes
Secondary	Rifampicin plasma concentration dosage		2 months	No

External Links

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