Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
Recruitment status was Active, not recruiting
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
![](https://webarchive.library.unt.edu/web/20130305101217im_/http://clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
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.
Condition | Intervention |
---|---|
HIV Infections Tuberculous Meningitis |
Drug: Combivir and efavirenz |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
Official Title: | Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis |
- Mortality [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- Mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Fever clearance time [ Designated as safety issue: No ]
- Coma clearance time [ Designated as safety issue: No ]
- CD4 count [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- plasma HIV RNA [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Grade 3 or 4 adverse event [ Time Frame: Any ] [ Designated as safety issue: Yes ]
- Neurological disability [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Enrollment: | 253 |
Study Start Date: | September 2005 |
Estimated Study Completion Date: | December 2008 |
Estimated Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Experimental: 1
Combivir, efavirenz for 12 months
|
Drug: 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: 2
Placebo for 2 months followed by Combivir and efavirenz for 10 months
|
Drug: Combivir and efavirenz
Arm 1: Combivir and efavirenz for 12 months Arm 2: Placebo for 2 months then Combivir and efavirenz for 10 months
|
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.
![](https://webarchive.library.unt.edu/web/20130305101217im_/http://clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
Ages Eligible for Study: | 15 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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.
![](https://webarchive.library.unt.edu/web/20130305101217im_/http://clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
Vietnam | |
Hospital for Tropical Diseases | |
Ho Chi Minh City, Vietnam | |
Pham Ngoc Thach Hospital | |
Ho Chi Minh City, Vietnam |
Principal Investigator: | Estee Torok | University of Oxford |
![](https://webarchive.library.unt.edu/web/20130305101217im_/http://clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
No publications provided
Responsible Party: | Centre for Tropical Diseases, University of Oxford |
ClinicalTrials.gov Identifier: | NCT00433719 History of Changes |
Other Study ID Numbers: | OXTREC 023-04, ISRCTN63659091 |
Study First Received: | January 25, 2007 |
Last Updated: | August 6, 2008 |
Health Authority: | United Kingdom: Research Ethics Committee Vietnam: Ho Chi Minh City Health Service |
Keywords provided by University of Oxford:
Human immunodeficiency virus Tuberculous meningitis Treatment Naive |
Additional relevant MeSH terms:
HIV Infections Acquired Immunodeficiency Syndrome Meningitis Tuberculosis Tuberculosis, Meningeal Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Central Nervous System Infections |
Central Nervous System Diseases Nervous System Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Meningitis, Bacterial Central Nervous System Bacterial Infections Tuberculosis, Central Nervous System Efavirenz Lamivudine, zidovudine drug combination Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on March 03, 2013