Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00433719
Status:
UNKNOWN
Last Update Posted:
2008-08-07
First Post:
2007-01-25
Brief Title:
Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
Status:
UNKNOWN
Status Verified Date:
2008-06
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 03 - 04mgkg will be administered and tapered over 6 - 8 weeks according to TBM grade
Antiretrovira l treatment Antiretrovirals zidovudine lamivudine and efavirenzor 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
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 03 - 04mgkg will be administered and tapered over 6 - 8 weeks according to TBM grade
Antiretrovira l treatment Antiretrovirals zidovudine lamivudine and efavirenzor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ISRCTN63659091 | None | None | None |