Table 1.

Registered current and future trials in tuberculosis meningitis, listed by start date

Trial short title	Design	Study population	Intervention arms(s)	Countries recruiting	Sample size	Recruitment period	Primary outcome	Clinical trial registry number
TBM-KIDS	Randomised, open-label trial phase II	Age ≥6 months Age < 12 years Weight >6 kg Clinical TBM	Control: standard anti-TB therapy Interventions: High-dose rifampicin (30 mg/kg) containing regimen, OR high dose rifampicin (30 mg/kg) containing regimen plus substitution of ethambutol for levofloxacin (20 mg/kg)	India, Malawi	120	February 2017 -- ongoing	PK, functional, neurocognitive and safety endpoints	NCT02958709
ACT HIV	Randomised, double blind, placebo controlled phase III trial	Age ≥18 years Clinical TBM HIV co-infected	Control: standard of care without dexamethasone Intervention: adjunctive dexamethasone tapering regimen	Vietnam, Indonesia	520	June 2017 -- ongoing	Overall survival until 12 months	NCT03092817
RiFT	Randomised, open-label, phase II trial	Age ≥18 years Clinical TBM	Control: standard anti-TB therapy Interventions: regimens containing high dose (20 mg/kg) intravenous then oral 35 mg/kg rifampicin OR high dose (35 mg/kg) oral rifampicin	Uganda	60	September 2017 -- ongoing	PK parameters, composite safety endpoint	ISRCTN 42218549
LAST ACT	LTA4H genotype stratified, randomised (CC or CT genotypes), double blind, placebo-controlled phase III noninferiority trial	Age ≥18 years Clinical TBM HIV-uninfected	Control: standard of care without dexamethasone Intervention: adjunctive dexamethasone tapering regimen	Vietnam	720	February 2018 -- ongoing	All-cause mortality or new neurological event until 12 months	NCT03100786
Optimizing anti-TB therapy in adults with TBM	NAT2 stratified, randomised, parallel group trial	Age 18–65 years Clinical TBM	Control: standard anti-TB therapy in normal acetylators Interventions: rapid acetylators randomised to standard isoniazid containing regimen OR high dose isoniazid containing regimen	China	676	March 2019 -- ongoing	Number of participants with death or severe disability at 12 months	NCT03787940
LASER-TBM	Randomised, parallel group, multiarm phase IIa trial	Age ≥18 years Clinical TBM HIV co-infected	Control: standard anti-TB therapy Interventions: high-dose regimen containing 35 mg/kg oral rifampicin, and oral linezolid 1.2 g, OR high-dose regimen plus aspirin 1 g	South Africa	100	June 2019 -- ongoing	Treatment related adverse events	NCT03927313
SIMPLE	Randomised, open label phase II trial	Age ≥18 years Clinical TBM	control: anti-TB regimen containing 35 mg/kg rifampicin (high dose) Interventions: High-dose rifampicin regimen with oral linezolid 600 mg, OR high-dose rifampicin regimen with oral linezolid 1.2 g	Indonesia	36	June 2019 -- ongoing	Linezolid blood and CSF PK	NCT03537495
HARVEST	Randomised, double-blinded, placebo-controlled, phase III trial	Age ≥18 years Clinical TBM	Control: standard fixed dose anti-TB therapy Intervention: Regimen containing additional four oral rifampicin 300 mg capsules	Indonesia, South Africa, Uganda	500	Estimated recruitment start - January 2020	6-month survival	ISRCTN 15668391
SURE	Multifactorial randomiization (×2), open label phase III trial	Age >28 days Age <15 years Clinical TBM	Control: standard 12-month anti-TB therapy Interventions: 6-month intensified therapy Oral aspirin 20 mg/kg or placebo	India, Uganda, Vietnam, Zambia, Zimbabwe	400	Estimated recruitment start - February 2020	All-cause mortality at 48 weeks, neuro-development at 48 weeks	ISRCTN40829906
ALTER	Randomised, open-label, phase II trial	Age >18 years Clinical TBM	Four arms: standard dose rifampicin containing regimen with/without oral linezolid 1.2 g, or high-dose (35 mg/kg) rifampicin with/without oral linezolid 1.2 g	Uganda	60	Estimated recruitment start -- April 2020	CSF PK	NCT04021121
INTENSE- TBM	Randomised, placebo controlled (for aspirin), phase III, 2 × 2 factorial superiority trial	Age ≥15 years Clinical TBM	Four arms: standard anti-TB therapy OR high dose (35 mg/kg) oral rifampicin containing therapy and plus oral linezolid 1.2 g added to standard anti-TB therapy, with/without aspirin 200 mg	Ivory Coast Madagascar South Africa Uganda	768	Estimated recruitment start -- April 2020	Rate of all-cause death until 40 weeks	NCT04145258

CSF, cerebrospinal fluid; ISRCTN, prefix to unique clinical trials number in the International Standard Randomised Controlled Trial Number registry; LTA4H, leukotriene A4 hydrolase; NAT2, N-acetyltransferase type 2; NCT, prefix to unique clinical trials number on clinicaltrials.gov; PK, pharmacokinetic; TBM, tuberculous meningitis.