Data category	Information
Primary registry and trial identifying number	ClinicalTrials.gov NCT04145258
Date of registration in primary registry	30 October 2019
Secondary identifying numbers	ANRS 12398 INTENSE-TBM
Source(s) of monetary or material support	European and Developing Countries Clinical Trials Partnership (EDCTP)
Primary sponsor	ANRS Emerging Infectious Diseases
Contact for public queries	VM, université de Bordeaux (vanessa.machault@u-bordeaux.fr; contact@intense-tbm.org) FE, Programme PAC-CI (frederic.ello@pac-ci.org)
Contact for scientific queries	FB, université de Bordeaux, CHU de Bordeaux (fabrice.bonnet@chu-bordeaux.fr; contact@intense-tbm.org) FE, Programme PAC-CI (frederic.ello@pac-ci.org)
Public title	Intensified Tuberculosis Treatment to Reduce the Mortality of Patients With Tuberculous Meningitis (INTENSE-TBM)
Scientific title	Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis: a phase III randomized controlled trial
Countries of recruitment	Ivory Coast, Madagascar, Uganda, South Africa
Health condition(s) or problem(s) studied	Tuberculous meningitis
Intervention(s)	Drug: Aspirin Drug: Placebo of aspirin Drug: WHO TBM treatment Drug: Intensified TBM treatment
Key inclusion and exclusion criteria	Ages eligible for study: ≥15 years Sexes eligible for study: both Accepts healthy volunteers: no
	Inclusion criteria: age ≥ 15 years, TBM defined as “definite”, “probable” or “possible”, using criteria proposed by the Tuberculosis Meningitis International Research Consortium, Informed consent signed by the patient.
	Exclusion criteria: having received >5 days of TB treatment, renal failure (eGFR<30 ml/min, CKD-EPI formula), neutrophil count < 0.6 × 109/L, hemoglobin concentration < 8 g/dL, platelet count < 50 × 109/L, ALT > 5 times the Upper Limit of Normal, clinical evidence of liver failure or decompensated cirrhosis, for women: more than 17 weeks pregnancy or breastfeeding, for patients without decrease level of consciousness (Glasgow Coma Scale = 15): Peripheral neuropathy scoring Grade 3 on the Brief Peripheral Neuropathy Score (BPNS), documented M. tuberculosis resistance to rifampicin, positive gram-stain, bacterial culture or cryptococcal antigen in the cerebrospinal fluid or blood, evidence of active bleeding (hemoptysis, gastrointestinal bleeding, hematuria, intracranial bleeding), inability to collect cerebrospinal fluid, except for patients with confirmed tuberculosis (by rapid molecular test or culture) from another biological sample and clinical and/or CT scan evidence of meningitis, major surgery within the last two weeks prior to inclusion, ongoing chronic aspirin treatment (e.g., for cardiovascular risk), current use of drugs contraindicated with study drugs and that cannot be safely stopped, in available history from patients: evidence of past intracranial bleeding; evidence of past of peptic ulceration; evidence of recent (< 3 months) gastrointestinal bleeding; known hypersensitivity contraindicating the use of study drugs (aspirin, rifampicin, linezolid, isoniazid, pyrazinamide, ethambutol); evidence of porphyria, any reason which at the discretion of the investigator would compromise safety and cooperation in the trial.
Study type	Interventional
	Allocation: randomized intervention model. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). The trial is open-label for anti-TB treatment and placebo-controlled for aspirin treatment.
	Primary purpose: treatment
	Phase III
Date of first enrolment	February 2021
Target sample size	768
Recruitment status	Recruiting
Primary outcome(s)	Rate of all-cause death [time grame: up to 40 weeks]
Key secondary outcomes	Rate of all-cause death [time frame: up to 8 weeks] Rate of all-cause death or loss to follow up [time frame: up to 40 weeks] Rate of new central neurological event or aggravation of a central neurological event existing at baseline [time Frame: up to 40 weeks] Rate of grade 3–4 adverse events (DAIDS adverse events grading table) [time frame: up to 40 weeks ]