Overview

This trial is active, not recruiting.

Condition tuberculous meningitis
Treatments 81mg aspirin, 1000mg aspirin, placebo
Phase phase 2
Sponsor Oxford University Clinical Research Unit, Vietnam
Collaborator Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Start date October 2014
End date December 2016
Trial size 120 participants
Trial identifier NCT02237365, 23TB

Summary

Tuberculous meningitis is a severe brain infection which often causes disability and death even when treated with the best available treatment. Aspirin is a type of anti-inflammation drug which can reduce the inflammatory response in brains of patients with tuberculous meningitis, and therefore may decrease some of the most severe outcomes. This study compares the use of aspirin (at 2 different doses) versus placebo as an additional therapy to the standard treatment to see if aspirin is safe and helpful in reducing disability and death from tuberculous meningitis. Patients will be treated with aspirin or placebo for 60 days and followed up while on standard treatment for 8 months.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Aspirin 81mg daily for 60 days
81mg aspirin
1 tablet of 81mg aspirin and 2 tablets of placebo (visually matched to 500mg aspirin) daily for 60 days
(Experimental)
Aspirin 1000mg daily for 60 days
1000mg aspirin
1 tablet of 81mg placebo (visually matched to 81mg aspirin) and 2 tablets of 500mg aspirin daily for 60 days
(Placebo Comparator)
Visually matched placebo daily for 60 days
placebo
1 tablet of 81mg placebo (visually matched to 81mg aspirin) and 2 tablets of 500mg placebo (visually matched to 500mg aspirin) daily for 60 days

Primary Outcomes

Measure
Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint)
time frame: 60 days
Number of episodes of MRI-proven brain infarction or death (composite endpoint)
time frame: 60 days

Secondary Outcomes

Measure
Time to death
time frame: 240 days
Number of grade 3&4 and serious adverse events
time frame: 60 days
Duration of hospital stay
time frame: 240 days
Neurological disability score
time frame: 60 days
Neurological disability score
time frame: 240 days
Resolution of cerebrospinal fluid (CSF) inflammation
time frame: 30 days
Antimicrobial activity of peripheral blood monocyte/macrophages
time frame: 240 days
Proportion of patients with MRI-proven brain infarction
time frame: 240 days

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female, aged 18 years or above. - Suspected TBM and anti-tuberculosis chemotherapy either planned or started - Less than 3 days of anti-tuberculosis chemotherapy taken for the current infection - Patient or representative (if the patient is unable) is willing and able to give informed consent for participation in the study. Exclusion Criteria: - HIV infection (negative rapid test or Elisa test is required) - Unlikely, for any reason, to be able to have an MRI brain scan within 5 days (120 hours) of randomisation - Known or suspected infection with multi-drug resistant tuberculosis (resistant to at least isoniazid and rifampicin) - Unable to take isoniazid, rifampicin, or pyrazinamide at recommended doses for any reason - History of diagnosed peptic ulceration or gastro-intestinal bleeding - Active gastro-intestinal bleeding is suspected - Taken >1 dose of aspirin (at any dose) or any other non-steroidal anti-inflammatory drugs for any reason within 2 weeks of screening - Aspirin considered mandatory for any reason by the attending physician - Aspirin considered to be contraindicated for any reason by the attending physician - Pregnancy or breast feeding (negative urine pregnancy test for all females of child-bearing age) - Dexamethasone considered to be contraindicated for any reason by the attending physician - Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

Additional Information

Official title A Pilot Phase II Randomized Controlled Double Blind Trial of 81mg Aspirin Daily vs. 1000 mg Aspirin Daily vs. Placebo as Adjunctive Therapy in HIV Negative Adults With Tuberculous Meningitis
Principal investigator Guy Thwaites, MD, PhD
Description The study is a parallel group, double blind, randomised, placebo controlled trial of 60 days treatment with placebo vs. 81mg daily dose vs. 1000mg daily dose aspirin for the treatment of HIV-uninfected adults with tuberculous meningitis. All patients will receive standard anti-tuberculous chemotherapy and adjunctive dexamethasone, according to Viet Nam National Tuberculosis Programme guidelines. Participants will be stratified by Medical Research Council UK disease severity grade, and randomized at enrollment to one of three study arms (1:1:1 ratio). Patients will be admitted to hospital for at least the first 14 days of study treatment enabling real-time active surveillance of any adverse events after which they will be discharged according to clinical care with continued monitoring. A schedule of clinical and laboratory monitoring including lumbar puncture, pharmacokinetic assessment of peripheral blood monocyte/macrophage antimicrobial activity, clinical assessments, brain magnetic resonance imaging (MRI) and neurological assessment will manage patient safety and capture study outcomes.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Oxford University Clinical Research Unit, Vietnam.