Trial record 18 of 28 for:    " January 24, 2007":" February 23, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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
  Purpose

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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Mortality [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433719

Locations
Vietnam
Hospital for Tropical Diseases
Ho Chi Minh City, Vietnam
Pham Ngoc Thach Hospital
Ho Chi Minh City, Vietnam
Sponsors and Collaborators
University of Oxford
Wellcome Trust
Investigators
Principal Investigator: Estee Torok University of Oxford
  More Information

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 August 01, 2014