Clinical trial NCT00533390: Randomized Clinical Trial to Assess the Efficacy and Safety of Concomitant Use of Rifampicin and Efavirenz 600 X 800mg
Official title: Anti-retroviral Efficacy, Tolerance and Other Pharmacologic Interactions of the Non Nucleoside Analog Efavirenz in Association With Rifampicin to Treat Tuberculosis and AIDS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Tuberculosis
HIV Infections
Keywords: efavirenz
tuberculosis
AIDS
rifampicin
efficacy
safety
Treatment Naive
Lead sponsor: Oswaldo Cruz Foundation
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
First posted: 2007-09-21
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: proportion of patients with viral load < 80 at the end of tuberculosis therapy proportion of adverse events in each group
timeFrame: 6 months
Secondary outcomes:
measure: Immunologic reconstitution Genotyping resistance
timeFrame: 6 months
Other outcomes:
Locations:
city: Vitoria
country: Brazil
facility: Universidade Federal do Espirito Santo
state: Espirito Santo
city: Rio de Janeiro
country: Brazil
facility: FIOCRUZ Instituto de Pesquisa Clinica Evandro Chagas
Study officials:
affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz
name: Valeria C Rolla, MD DSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz
name: Maria Cristina S Lourenço, MSc
role: STUDY_CHAIR
affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz
name: Flávia M Sant'Anna, MSc
role: STUDY_CHAIR
affiliation: Instituto Oswaldo Cruz, Fiocruz
name: Mariza G Morgado, DSc
role: STUDY_CHAIR
affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz
name: Pedro E Americano do Brasil, MD MSc
role: STUDY_CHAIR
affiliation: Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz
name: Carolina S Smaltz, PhD student
role: STUDY_CHAIR
affiliation: Instituto de pesquisa Clinica Evandro Chagas
name: Jose L Teixeira, Pharmacist
role: STUDY_CHAIR
affiliation: Federal University of Espirito Santo
name: David J Hadad, PhD
role: STUDY_CHAIR
affiliation: Federal University of Espirito Santo
name: Reynaldo Dietze, PhD
role: STUDY_CHAIR
affiliation: Federal University of Espirito Santo
name: Moises Palaci, PhD
role: STUDY_CHAIR
References: