A Randomised Trial To Assess The Efficacy Of Add On Therapy With Aspirin Or Clopidogrel To The Standard Medical Therapy Alone In Patients With Tubercular Meningitis: ACT TBM

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis and can be complicated with occurrence of cerebral infraction or stroke adding on to the morbidity and mortality. Ischemic stroke (IS) is a serious complication of TBM and usually affects the small and medium size intracranial vessels. The presumed mechanism(s) are believed to be either inflammation secondary to an endarteritis or a prothrombotic effect or both. Two adult studies on TBM have suggested a benefit of aspirin therapy on reduction of cerebral infarction and mortality. However, the trials were limited by small sample sizes and methodology issues. Therefore, a phase 3 trial with adequate sample size and follow up is necessary. The present study is planned as a multicentric (two centre) phase 3 prospective randomised open label trial with blinded outcome assessment (PROBE design). Adult patients with a diagnosis of TBM and fulfilling inclusion criteria shall be randomly allocated to one of the three arms: standard ATT and steroids, standard ATT, steroids and add on aspirin 75mg/day or standard ATT, steroids and clopidogrel 75mg/day. Both aspirin and clopidogrel shall be given for a period of 3 months. All patients will be followed up for a period of 6 months. The primary outcome shall be any new onset cerebral infarction on MRI scan or development of clinical stroke at one and 3 months. The secondary outcome shall be mortality at 3 months and modified Rankin score at 3 and 6 months. Safety outcomes will include any major or minor bleeding event. This will help understand the benefit or harm of antiplatelet intervention in this condition and may also help us observe whether anti-inflammatory effect alone or antiplatelet effect of these agents are responsible for any benefit if observed.