HIV InfectionsNCT00433719
Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
A study testing Combivir and efavirenz in people with HIV Infections and Tuberculous Meningitis, run by University of Oxford at 2 sites in Vietnam.
Trial 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). Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- HIV Infections, Tuberculous Meningitis
- What is being tested?
- Combivir and efavirenz
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 253 participants
- Where
- 2 sitesVietnam
- Study dates
- Sep 2005to Dec 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- age 15 years or older
- HIV antibody positive
- clinical diagnosis of TB meningitis
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Vietnam2 sites
Hospital for Tropical Diseases
Ho Chi Minh City
Pham Ngoc Thach Hospital
Ho Chi Minh City
About this study
Official title: 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.
Read the 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.
- Conditions
- HIV Infections, Tuberculous Meningitis
- Being tested
- Combivir and efavirenz
- Keywords
- Human immunodeficiency virus, Tuberculous meningitis, Treatment Naive
- Medical subject headings
- HIV Infections, Tuberculosis, Meningeal, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combivir and efavirenzDrug
Arm 1: Combivir and efavirenz for 12 months Arm 2: Placebo for 2 months then Combivir and efavirenz for 10 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Combivir, efavirenz for 12 months Receives: Drug: Combivir and efavirenz |
| 2 | Placebo comparator | Placebo for 2 months followed by Combivir and efavirenz for 10 months Receives: Drug: Combivir and efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Measured: 9 months
Secondary outcomes (7)
Mortality
Measured: 12 months
Fever clearance time
Coma clearance time
CD4 count
Measured: 12 months
plasma HIV RNA
Measured: 12 months
Grade 3 or 4 adverse event
Measured: Any
Neurological disability
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2007 (estimated)
- Study startSep 2005
- Primary completionDec 2008 (estimated)
- Study completionDec 2008 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 253 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Investigators
- Estee Torok, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00433719
- Sponsor's protocol ID
- OXTREC 023-04
- Other IDs
- ISRCTN63659091
- Status last verified
- Jun 2008
- First submitted
- 25 Jan 2007
- Last updated
- 7 Aug 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
- ClinicalTrials.gov ID
- NCT00433719
- Acronym / sponsor ID
- OXTREC 023-04
- Conditions
- HIV Infections, Tuberculous Meningitis
- Keywords
- Human immunodeficiency virus, Tuberculous meningitis, Treatment Naive
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 253 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- Sep 2005
- Primary completion
- Dec 2008 (estimated)
- Study completion
- Dec 2008 (estimated)
- First posted
- 12 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Combivir and efavirenzCombivir, efavirenz for 12 months |
| 2 | Placebo comparator | Drug: Combivir and efavirenzPlacebo for 2 months followed by Combivir and efavirenz for 10 months |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- age 15 years or older
- HIV antibody positive
- clinical diagnosis of TB meningitis
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combivir and efavirenzArm 1: Combivir and efavirenz for 12 months Arm 2: Placebo for 2 months then Combivir and efavirenz for 10 months | Drug | 1, 2 |
Primary outcome
Mortality
Time frame: 9 months
7 secondary outcomes
Mortality
Time frame: 12 months
Fever clearance time
Coma clearance time
CD4 count
Time frame: 12 months
plasma HIV RNA
Time frame: 12 months
Grade 3 or 4 adverse event
Time frame: Any
Neurological disability
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Estee Torok principal investigator
University of Oxford
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combivir and efavirenz in people with HIV Infections and Tuberculous Meningitis, run by University of Oxford at 2 sites in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2008.