This two-stage study will compare consented research participants with tuberculous meningitis receiving BPaLMZ to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), known as RHZE.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
312
bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide
Infectious Diseases Institute
Kampala, Uganda
RECRUITINGMbarara University of Science and Technology
Mbarara, Uganda
RECRUITINGTime to Death
Time frame: 24 Weeks
Hierarchical composite endpoint (survival + functional status)
Hierarchical composite endpoint of survival and modified Rankin score (0-6 scale) assessed by Win Ratio
Time frame: 24 Weeks
Serious adverse events (SAE)
Incidience of Serious adverse events
Time frame: 28 weeks
Clinical Adverse Events
Clinical Adverse Events, by grade (1-5) associated with TB drug discontinuation, dose reduction, or interruption \>3 days
Time frame: 28 weeks
Laboratory abnormalities
Number of participants with grade 3 or 4 abnormal laboratory values, by the Division of AIDS toxicity grading scale
Time frame: 28 weeks
Neuropathy
Incidence of Neuropathy
Time frame: 28 weeks
Drug induced liver injury
Drug induced liver injury with Grade \>=3 with serum alanine aminotransferase (ALT) \>5x upper limit or normal or total bilirubin \>2.5x upper limit of normal)
Time frame: 28 weeks
Change in CSF inflammatory markers
Change in CSF leukocytes from baseline to day 7 and 14 visits.
Time frame: 14 days
Modified Rankin Scale
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Modified Rankin Score as an ordinal score (0-6 scale) of: 0 Alive: no residual symptoms or disability. 1. No significant disability: symptoms are present but do not prevent carrying out all usual duties and activities; able to carry out all pre-TBM activities. 2. Slight disability: unable to carry out all pre-TBM activities but able to look after self without daily help. 3. Moderate disability: requires some assistance with tasks but able to walk without assistance. 4. Moderately severe disability: unable attend to bodily functions or walk without assistance. 5. Severe disabilities: bedridden, incontinent, requires continuous care and attention. 6. Dead
Time frame: 24 weeks
Change in blood inflammatory markers
Change in white blood cell count from baseline to day 7 visit
Time frame: 7 days
Quantitative neurocognitive performance Z-score
Quantitative neurocognitive performance Z-score scaled to Ugandan population adult norms where population average = 0. Performance is Z-scored such that performance that is one standard deviation better than average is +1 and one standard deviation worse is -1.
Time frame: 24 weeks
Change in PCR cycle threshold (Ct) value in CSF
Change in PCR cycle threshold (Ct) value in CSF from baseline to Day 7 and 14 visits.
Time frame: 14 days
Altered Mental Status over time
Number of days with Glasgow Coma Scale score = 15 within the first 10 days
Time frame: 10 days
Additional corticosteroids use
Additional corticosteroids use in TBM survivors (beyond initial use)
Time frame: 24 weeks
Change in CSF glcuose
Change in CSF glcuose from baseline to day 7 to day 14
Time frame: 14 days
Change in serum C-reactive protein
Change in serum C-reactive protein (CRP) from baseline to day 7
Time frame: 7 days