Overview

This trial is active, not recruiting.

Conditions hiv infections, tuberculous meningitis
Treatment combivir and efavirenz
Sponsor University of Oxford
Collaborator Wellcome Trust
Start date September 2005
End date December 2008
Trial size 253 participants
Trial identifier NCT00433719, ISRCTN63659091, OXTREC 023-04

Summary

The optimal time to initiate antiretroviral therapy (ART) in HIV-associated tuberculous meningitis (TBM) unknown. There are concerns that immediate ART may worsen rather than improve outcome, because drug interactiond and toxicities or development of an intracerebral immune reconstitution inflammatory syndrome (IRIS). Conversely, delaying ART may result in increased HIV-related deaths. To answer this question, we are conducting a randomised, double-blind placebo-controlled trial comparing immediate and deferred ART in HIV-infected patients presenting with TBM, to assess effect on survival.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Combivir, efavirenz for 12 months
combivir and efavirenz
Arm 1: Combivir and efavirenz for 12 months Arm 2: Placebo for 2 months then Combivir and efavirenz for 10 months
(Placebo Comparator)
Placebo for 2 months followed by Combivir and efavirenz for 10 months
combivir and efavirenz
Arm 1: Combivir and efavirenz for 12 months Arm 2: Placebo for 2 months then Combivir and efavirenz for 10 months

Primary Outcomes

Measure
Mortality
time frame: 9 months

Secondary Outcomes

Measure
Mortality
time frame: 12 months
Fever clearance time
time frame:
Coma clearance time
time frame:
CD4 count
time frame: 12 months
plasma HIV RNA
time frame: 12 months
Grade 3 or 4 adverse event
time frame: Any
Neurological disability
time frame: 12 months

Eligibility Criteria

Male or female participants at least 15 years old.

Inclusion Criteria: - age 15 years or older - HIV antibody positive - clinical diagnosis of TB meningitis Exclusion Criteria: - positive CSF Gram or India ink stain - known or suspected pregnancy - antituberculous treatment 8 - 30 days immediately prior to recruitment - previous antiretroviral therapy - laboratory contraindications to antiretroviral or antituberculous therapy - lack of consent.

Additional Information

Official title Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
Principal investigator Estee Torok
Description Title: Study of immediate versus deferred antiretroviral therapy in HIV-associated tuberculous meningitis Study design: A randomized, double blind, placebo-controlled trial with 2 parallel arms Sample size: 247 Inclusion criteria: Age 15 years or older; HIV antibody positive; clinical diagnosis of TBM. Exclusion criteria: positive CSF Gram or India ink stain, known or suspected pregnancy; antituberculous treatment 8 to 30 days immediately prior to recruitment; previous antiretroviral therapy; laboratory contraindications to antiretroviral or antituberculous therapy; lack of consent. Consent: Written informed consent will be sought for all patients. Verbal consent will be considered acceptable when written consent is impossible. In unconscious patients, the consent of 2 independent physicians will be considered acceptable. Randomization: Patients will be stratified according to TBM disease severity at presentation (modified MRC grade I to III). Within each stratum, patients will be randomized to 1 of the 2 treatment arms: immediate or deferred (2 months) ART. Antituberculous treatment: Initial therapy will be with isonazid, rifampicin, pyrazinamide and ethambutol for 3 months. After 3 months, patients will continue on rifampicin and isoniazid for a further 6 months. Corticosteroid treatment: Dexamethasone 0.3 - 0.4mg/kg will be administered and tapered over 6 - 8 weeks, according to TBM grade. Antiretrovira l treatment: Antiretrovirals (zidovudine, lamivudine and efavirenz)or identical placebo tablets will be commenced at study entry and continued for 2 months. Thereafter, all patients will received antiretrovirals. Clinical monitoring: Patients will be assessed weekly as an inpatient for 3 months. Hospital outpatient review will occur monthly until 9 months. A final follow-up visit will take place at 12 months. Laboratory monitoring: Routine laboratory tests will be monitored weekly as an inpatient and monthly as an outpatient. Blood samples for CD4 T-lymphocyte count and plasma HIV-1 RNA level will be monitored 3-monthly. CSF samples will be taken at 0, 1, 2, 3, 6 and 9 months. Radiology: Patients will have a chest radiograph performed on admission. A CT or MRI brain scan may also be performed if clinically indicated. Adverse events: All grade 3 and 4 adverse events will be reported immediately to the Data and Safety Monitoring Committee. Outcome measures: The primary endpoint will be mortality at 9 months. The secondary endpoints will be: mortality at 12 months; fever clearance time; coma clearance time; neurological relapse; progression to new or recurrent AIDS defining illness; any grade 3 or 4 adverse event; CD4 count response; plasma HIV-1 RNA response; neurological disability. Data analysis: Analysis will be based on intention to treat.
Trial information was received from ClinicalTrials.gov and was last updated in August 2008.
Information provided to ClinicalTrials.gov by University of Oxford.