High-dose Rifampicin for the Treatment of Tuberculous Meningitis: a Dose-finding Study
Status:
Completed
Trial end date:
2017-05-05
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Universitas Padjadjaran
Collaborators:
Radboud University United States Agency for International Development (USAID)