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Tracking Information | |||||
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First Received Date † | January 25, 2007 | ||||
Last Updated Date | August 6, 2008 | ||||
Start Date † | September 2005 | ||||
Current Primary Outcome Measures † |
Mortality [ Time Frame: 9 months ] [ Designated as safety issue: No ] | ||||
Original Primary Outcome Measures † | Same as current | ||||
Change History | Complete list of historical versions of study NCT00433719 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures † |
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Original Secondary Outcome Measures † | Same as current | ||||
Descriptive Information | |||||
Brief Title † | Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis | ||||
Official Title † | Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis | ||||
Brief 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. |
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Detailed 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. |
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Study Phase | |||||
Study Type † | Interventional | ||||
Study Design † | Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study | ||||
Condition † |
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Intervention † | Drug: Combivir and efavirenz | ||||
Study Arms / Comparison Groups |
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Publications * | |||||
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline. |
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Recruitment Information | |||||
Recruitment Status † | Active, not recruiting | ||||
Enrollment † | 253 | ||||
Estimated Completion Date | December 2008 | ||||
Estimated Primary Completion Date | December 2008 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria † | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||
Ages | 15 Years and older | ||||
Accepts Healthy Volunteers | No | ||||
Contacts †† | |||||
Location Countries † | Vietnam | ||||
Expanded Access Status | |||||
Administrative Information | |||||
NCT ID † | NCT00433719 | ||||
Responsible Party | Centre for Tropical Diseases, University of Oxford | ||||
Secondary IDs †† | ISRCTN63659091 | ||||
Study Sponsor † | University of Oxford | ||||
Collaborators †† | Wellcome Trust | ||||
Investigators † |
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Information Provided By | University of Oxford | ||||
Verification Date | June 2008 | ||||
† Required WHO trial registration data element. †† WHO trial registration data element that is required only if it exists. |