Tuberculosis, Meningeal Clinical Trial
Official title:
A Randomized Double Blinded Phase 2b Clinical Trial Comparing Standard Dose With Two Higher Doses of Rifampicin for Treatment of Adults With Tuberculous Meningitis
Tuberculous meningitis (TBM) is the most severe form of tuberculosis infection with high
mortality. Current treatment regimens are not based on clinical trials. Rifampicin is a key
drug for TBM, but its penetration into the brain is limited, suggesting that a higher dose
may be more effective.
There are several highly relevant, outstanding questions related to the appropriate dose of
rifampicin for TBM, before a multicenter phase 3 trial can be performed. These are:
1. Previous phase 2a randomized clinical trial (done in the same setting as this proposed
study) suggests that high doses of intravenous rifampicin (600mg, circa 13 mg/mg) for
TBM is safe and associated with a survival benefit in adults. Given that i.v.
rifampicin is not readily available, this needs to be confirmed using an equivalent
higher oral dose of rifampicin.
2. Recent pharmacokinetic analysis of a continuation trial comparing 600 mg i.v.
rifampicin with 750 mg and 900 mg oral rifampicin suggests that an even higher dose may
be needed; but this has not been examined
3. Based on those previous data, there is a need to explore a longer duration of high-dose
rifampicin for a subsequent phase 3 randomized clinical trial; treatment response in
the investigators previous trial suggest that the optimal duration may be > 14 days.
4. There is a need to explore relevant treatment endpoints besides mortality including
neurological, neuroradiological and inflammatory response.
n/a
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