B-PaLMZ for TB Meningitis

Hierarchical composite endpoint of survival and modified Rankin score (0-6 scale) assessed by Win Ratio

Incidience of Serious adverse events

Clinical Adverse Events, by grade (1-5) associated with TB drug discontinuation, dose reduction, or interruption >3 days

Number of participants with grade 3 or 4 abnormal laboratory values, by the Division of AIDS toxicity grading scale

Incidence of Neuropathy

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)

Change in CSF leukocytes from baseline to day 7 and 14 visits.

Modified Rankin Score as an ordinal score (0-6 scale) of:

0 Alive: no residual symptoms or disability.

• 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.
• Slight disability: unable to carry out all pre-TBM activities but able to look after self without daily help.
• Moderate disability: requires some assistance with tasks but able to walk without assistance.
• Moderately severe disability: unable attend to bodily functions or walk without assistance.
• Severe disabilities: bedridden, incontinent, requires continuous care and attention.
• Dead

Change in white blood cell count from baseline to day 7 visit

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.

Change in PCR cycle threshold (Ct) value in CSF from baseline to Day 7 and 14 visits.

Number of days with Glasgow Coma Scale score = 15 within the first 10 days

Additional corticosteroids use in TBM survivors (beyond initial use)

Change in CSF glcuose from baseline to day 7 to day 14

Change in serum C-reactive protein (CRP) from baseline to day 7