HIV Clinical Trial
Official title:
A Randomized Double Blind Placebo Controlled Trial of Adjunctive Dexamethasone for the Treatment of HIV-infected Adults With Tuberculous Meningitis
NCT number | NCT03092817 |
Other study ID # | 26TB |
Secondary ID | |
Status | Completed |
Phase | Phase 3 |
First received | |
Last updated | |
Start date | May 25, 2017 |
Est. completion date | April 26, 2023 |
Verified date | March 2024 |
Source | Oxford University Clinical Research Unit, Vietnam |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The investigators will conduct a randomized, double blind, placebo controlled trial of adjunctive dexamethasone in the initial (6-8 weeks) treatment of tuberculous meningitis in Vietnamese adults. The trial will address a primary hypothesis in all enrolled patients, and a secondary hypothesis in a sub-group of enrolled patients who develop anti-tuberculosis drug-induced liver injury (DILI). The primary hypothesis is adjunctive dexamethasone increases survival from TBM in HIV co-infected adults. The secondary hypothesis is current guidelines for the management of anti-tuberculosis drug-induced liver injury in those with TBM result in the premature interruption of rifampicin and isoniazid (the critical active drugs in early therapy) and are thereby placing participants at risk of poor outcomes.
Status | Completed |
Enrollment | 520 |
Est. completion date | April 26, 2023 |
Est. primary completion date | April 30, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Adult (18 years or older) - HIV-infected - Clinical diagnosis of TBM (=5 days of meningitis symptoms, and CSF abnormalities) and anti-tuberculosis chemotherapy either planned or started by the attending physician Note: Published diagnostic criteria will be applied to all enrolled participants at the end of the study when all mycobacterial culture results are available. The criteria will sub-divide all cases into definite, probable and possible TBM, and those with an alternative diagnosis. Exclusion Criteria: - An additional brain infection (other than TBM) confirmed or suspected: positive CSF Gram or India Ink stain; positive blood or CSF Cryptococcal antigen test; cerebral toxoplasmosis suspected and attending physician wants to give anti-toxoplasmosis treatment with anti-tuberculosis treatment - More than 6 consecutive days of two or more drugs active against M. tuberculosis immediately before screening - More than 3 consecutive days of any type of orally or intravenously administered corticosteroid immediately before randomisation - Dexamethasone considered mandatory for any reason by the attending physician - Dexamethasone considered to be contraindicated for any reason by the attending physician - Previously been randomised into the trial for a prior episode of TBM - Lack of consent from the participant or family member (if the participant is incapacitated by the disease) |
Country | Name | City | State |
---|---|---|---|
Indonesia | Cipto Mangunkusumo Hospital | Jakarta | |
Indonesia | Eijkman-Oxford Clinical Research Unit | Jakarta | |
Indonesia | RSUP Persahabatan Hospital | Jakarta | |
Vietnam | Hospital for Tropical Diseases | Ho Chi Minh City | |
Vietnam | Oxford University Clinical Research Unit | Ho Chi Minh City | |
Vietnam | Pham Ngoc Thach Hospital | Ho Chi Minh City |
Lead Sponsor | Collaborator |
---|---|
Oxford University Clinical Research Unit, Vietnam | Cipto Mangunkusumo Hospital, Jakarta, Indonesia, Eijkman Oxford Clinical Research Unit, Indonesia, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam, RSUP Persahabatan Hospital, Jakarta, Indonesia |
Indonesia, Vietnam,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Overall survival until 12 months after randomisation | The primary endpoint is overall survival, i.e. the time from randomization to death, during a follow-up period of 12 months. Survivors known to be alive at 12 months will be censored at that time-point and subjects who withdrew or were lost to follow-up before 12 months will be censored at the date they were last known to be alive. | 12 months from randomisation | |
Secondary | Neurological disability at 12 months (modified Rankin score) | Neurological disability will be assessed by the modified Rankin score (see below) on months 3, 6, 9, 12, 18 and 24 from randomisation. The main endpoint is the 12 month assessment and subjects who died before 12 months will be treated as having a score of 6 ('Dead').
The Modified Rankin Scale Score Description 0 No symptoms Minor symptoms not interfering with lifestyle Symptoms that lead to some restriction in lifestyle, but do not interfere with the patients ability to look after themselves Symptoms that restrict lifestyle and prevent totally independent living Symptoms that clearly prevent independent living, although the patient does not need constant care and attention. Totally dependent, requiring constant help day and night. Death |
at 12 months | |
Secondary | Time to new neurological event (defined as a fall in GCS of =2 points for =48 hours, new focal neurological sign, or new onset of seizures) or death by 12 months | A neurological event is defined as a fall in Glasgow coma score by =2 points for =2 days from the highest previously recorded Glasgow coma score (including baseline) or the onset of any of the following clinical adverse events: cerebellar symptoms, focal neurological signs, or onset of seizures. | by 12 months | |
Secondary | Rate of neurological IRIS events up to 6 months from randomisation | The rate is defined as the number of IRIS events divided by the observed person-time of follow-up in each treatment group. | 6 months from randomisation | |
Secondary | Time to new AIDS-defining illness or death by 12 months | AIDS-defining illnesses will be defined as per the WHO classification. | by 12 months | |
Secondary | Serious adverse events by 12 months | Comparison of the frequency of serious adverse events between treatment groups will form an important part of the study analysis. | by 12 months | |
Secondary | HIV-associated malignancy by 12 months | The three major HIV-associated malignancies are Kaposi sarcoma, high grade B-cell non-Hodgkin lymphoma and invasive cervical cancer. | by 12 months | |
Secondary | Overall survival | The main analysis of this trial will be performed at the time point where all randomized subjects have completed 12 months of follow-up. However, all participants will continue to be followed up for 24 months and overall survival will be reported once 24 month follow-up has been completed for all participants. | by 24 months | |
Secondary | Neurological disability | The main analysis of this trial will be performed at the time point where all randomized subjects have completed 12 months of follow-up. However, all participants will continue to be followed up for 24 months and neurological disability will be reported once 24 month follow-up has been completed for all participants. | by 24 months | |
Secondary | Time to new AIDS defining event or death | The main analysis of this trial will be performed at the time point where all randomized subjects have completed 12 months of follow-up. However, all participants will continue to be followed up for 24 months and this outcome will be reported once 24 month follow-up has been completed for all participants. | by 24 months | |
Secondary | Rate of HIV-related malignancy | The main analysis of this trial will be performed at the time point where all randomized subjects have completed 12 months of follow-up. However, all participants will continue to be followed up for 24 months and this outcome will be reported once 24 month follow-up has been completed for all participants. | by 24 months | |
Secondary | Recurrence of TBM within 24 months of follow-up | This outcome will be reported once 24 month follow-up has been completed for all participants. | 24 months |
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