The purpose of this study is to compare a 6-month regimen of high-dose rifampicin (RIF), high-dose isoniazid (INH), linezolid (LZD), and pyrazinamide (PZA) versus the World Health Organization (WHO) standard of care (SOC) treatment for tuberculosis meningitis (TBM).
Definite, probable, or possible TBM diagnosis wherein the participant is being committed to a full course of SOC anti-TB treatment for TBM in the setting of routine care. CSF, imaging, laboratory, and other results used to determine definite, probable, or possible TBM can be from testing performed as part of routine care, as long as obtained within 21 days prior to study entry
Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 30 days prior to study entry, OR
HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV-1 infection, or documentation of HIV diagnosis in the medical record by a healthcare provider
Documentation within 3 days prior to study entry of stage of disease using BMRC TBM grade.
More than 14 cumulative days of first-line TB medications, including but not limited to INH, RIF, EMB, and PZA, received within 90 days prior to study entry
Known current or previous drug resistant TB infection (i.e., resistance to one or more first-line TB medications, including but not limited to INH, RIF, EMB, LZD and PZA)
Known allergy/sensitivity or any hypersensitivity to components of study TB drugs (INH, RIF, LZD, PZA, and EMB) or their formulation
For participants who are able to undergo the Brief Peripheral Neuropathy Screen (BPNS) within 21 days prior to study entry, Grade 3 subjective peripheral neuropathy score on the BPNS AND EITHER vibratory loss OR absent ankle jerks
Parallel
Rifampicin (RIF)
DrugRifampicin 35 mg/kg
Isoniazid (INH)
DrugIsoniazid 10 or15 mg/kg
Linezolid (LZD)
Drug1200 mg
Pyrazinamide (PZA)
Drug25 mg/kg
ethambutol (EMB)
Drug20 mg/kg
Rifampicin
Drug10 mg/kg
Isoniazid
Drug5 mg/kg
Modified Rankin Scale (6-death, 5-severe disability, 4-moderately severe disability, 3-moderate disability, 2-slight disability, 1-no significant disability, 0-no symptoms)
Modified Rankin Scale (all 7 levels)
Modified Rankin Scale using collapsed categories: mRS (0 or 1), (2 or 3), (4 or 5), (6)
Modified Rankin Scale 5 or 6
Time to death through 48 and 72 weeks
Proportion of participants with recurrence
Positive or negative CSF Xpert Ultra
Positive or negative CSF and urine LAM
Functional outcomes and mortality in definite TBM patients
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