Randomized Clinical Trial to Assess the Efficacy and Safety of Concomitant Use of Rifampicin and Efavirenz 600 X 800mg

Phase 4

Terminated

• Conditions: Tuberculosis; HIV Infections
• Interventions: Drug: efavirenz

• Registration Number: NCT00533390
• Lead Sponsor: Oswaldo Cruz Foundation

Brief Summary

Rifampicin is a potent inducer of the CYP450 and decrease the plasmatic concentration of NNRTI and Protease Inhibitors. In our study we are going to compare the 600 an 800mg doses of efavirenz concomitant of rifampicin use to treat tuberculosis. The hypothesis is that the 800 mg dose would be more adequate than the 600mg

Detailed Description

The study consist in a open label randomized clinical trial comparing efavirenz 600mg QID versus efavirenz 800mg QID in patients with tuberculosis (treated with regimens including rifampicin) and AIDS diagnosis. The total duration of the study is 6 months for each patient. All eligible patient will be treated with a fist line regimen for tuberculosis according to Brazilian guidelines: rifampicin (600mg QID); isoniazid (400mg QID) e pyrazinamide (2g QID) during 6 months for a weight of 45 kg or more and adapted doses for persons with less than 45 kg. For patients with previous history of TB therapy etambutol 1.200mg QID will be added to the regimen.

Both groups will receive nucleoside reverse transcriptase inhibitors (NRTI)and a non nucleoside transcriptase inhibitor (NNRTI) to treat HIV. The ITRN of first choice will be zidovudine and lamivudine association. Patients presenting contra indication for the use of those drugs will receive others NRTI. The NNRTI is efavirenz (800 or 600mg).

Antiretrovirals will be initiated 30 days after stable TB therapy. In case of adverse events during TB therapy that lead to treatment interruption, the study drugs will be delayed until the 30th day after triple therapy for TB. During HIV therapy NRTI can be changed in case of intolerance

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2007-09-19
• Study First Submitted QC: 2007-09-20
• Study First Posted: 2007-09-21
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-07
• Last Update Posted: 2015-11-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Adults with tuberculosis diagnosis, HIV positive.
• Agreement to avoid not allowed drugs during the trial, agreement to participate in the study (informed consent)

Exclusion Criteria

• Active liver disease
• Pregnancy or breast feeding
• CD4 counts >350

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EFAVIRENZ 800mg	efavirenz	Efavirenz 800 mg (tablet) PO QD during 5 months associated with two nucleoside analogs during tuberculosis therapy with rifampicin
EFAVIRENZ 600mg	efavirenz	Efavirenz 600 mg (tablet) PO QD during 5 months associated with two nucleoside analogs during tuberculosis therapy with rifampicin

Primary Outcome Measures

Name	Time	Method
proportion of patients with viral load < 80 at the end of tuberculosis therapy proportion of adverse events in each group	6 months

Secondary Outcome Measures

Name	Time	Method
Immunologic reconstitution Genotyping resistance	6 months

Trial Locations

Locations (2)

FIOCRUZ Instituto de Pesquisa Clinica Evandro Chagas; 🇧🇷 Rio de Janeiro, Brazil

Universidade Federal do Espirito Santo; 🇧🇷 Vitoria, Espirito Santo, Brazil