Randomized Clinical Trial to Assess the Efficacy and Safety of Concomitant Use of Rifampicin and Efavirenz 600 X 800mg (IPEC-EFV)

Anti-retroviral Efficacy, Tolerance and Other Pharmacologic Interactions of the Non Nucleoside Analog Efavirenz in Association With Rifampicin to Treat Tuberculosis and AIDS

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

Study Overview

• Status: Terminated
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: efavirenz

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 Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 21040-900
    • FIOCRUZ Instituto de Pesquisa Clinica Evandro Chagas
  • Espirito Santo
    • Vitoria, Espirito Santo, Brazil
      • Universidade Federal do Espírito Santo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EFAVIRENZ 800mg; Efavirenz 800 mg (tablet) PO QD during 5 months associated with two nucleoside analogs during tuberculosis therapy with rifampicin	Drug: efavirenz; 600mg X 800mg QID during TB therapy with rifampicin associated with other antituberculosis drugs in patients concomitant treated for tuberculosis and AIDS; Other Names: Sustiva; Stocrin
Active Comparator: EFAVIRENZ 600mg; Efavirenz 600 mg (tablet) PO QD during 5 months associated with two nucleoside analogs during tuberculosis therapy with rifampicin	Drug: efavirenz; 600mg X 800mg QID during TB therapy with rifampicin associated with other antituberculosis drugs in patients concomitant treated for tuberculosis and AIDS; Other Names: Sustiva; Stocrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Immunologic reconstitution Genotyping resistance	6 months

Collaborators and Investigators

• Sponsor: Oswaldo Cruz Foundation
• Collaborators: Ministry of Health, Brazil
• Investigators: Principal Investigator: Valeria C Rolla, MD DSc, Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz; Study Chair: Maria Cristina S Lourenço, MSc, Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz; Study Chair: Flávia M Sant'Anna, MSc, Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz; Study Chair: Mariza G Morgado, DSc, Instituto Oswaldo Cruz, Fiocruz; Study Chair: Pedro E Americano do Brasil, MD MSc, Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz; Study Chair: Carolina S Smaltz, PhD student, Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz; Study Chair: Jose L Teixeira, Pharmacist, Instituto de Pesquisa Clínica Evandro Chagas; Study Chair: David J Hadad, PhD, Federal University of Espirito Santo; Study Chair: Reynaldo Dietze, PhD, Federal University of Espirito Santo; Study Chair: Moises Palaci, PhD, Federal University of Espirito Santo

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 19, 2007
• First Submitted That Met QC Criteria: September 20, 2007
• First Posted (Estimate): September 21, 2007

Study Record Updates

• Last Update Posted (Estimate): November 10, 2015
• Last Update Submitted That Met QC Criteria: November 7, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: safety; efficacy; AIDS; Treatment Naive; tuberculosis; efavirenz; rifampicin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz
• Other Study ID Numbers: CAAE-0017.1.009.000-03