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Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by University of Oxford.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Wellcome Trust
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00433719
First received: January 25, 2007
Last updated: August 6, 2008
Last verified: June 2008

January 25, 2007
August 6, 2008
September 2005
December 2008   (final data collection date for primary outcome measure)
Mortality [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Mortality at 9 months (end of TB treatment).
Complete list of historical versions of study NCT00433719 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV Infections
  • Tuberculous Meningitis
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
  • Experimental: 1
    Combivir, efavirenz for 12 months
    Intervention: Drug: Combivir and efavirenz
  • Placebo Comparator: 2
    Placebo for 2 months followed by Combivir and efavirenz for 10 months
    Intervention: Drug: Combivir and efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
253
December 2008
December 2008   (final data collection date for primary outcome measure)

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.
Both
15 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Vietnam
 
NCT00433719
OXTREC 023-04, ISRCTN63659091
Yes
Centre for Tropical Diseases, University of Oxford
University of Oxford
Wellcome Trust
Principal Investigator: Estee Torok University of Oxford
University of Oxford
June 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP