Rifampicin Explorative PK Study for Tuberculous Meningitis Comparing Oral and Intravenous Preparation

Summary

Tuberculous (TB) meningitis is the most severe manifestation of TB infection, leaving up to 50% of patients dead or neurologically disabled. Current treatment is similar to treatment of lung TB, although penetration of some antibiotics into the brain is poor and the immune-pathology of TB meningitis is very different from pulmonary TB. In a recent phase II clinical trial from the investigators group, the first of its kind globally, intensified antibiotic treatment, with moxifloxacin and high dose rifampicin, strongly reduced mortality of TB meningitis. The investigators aim to examine the effect of intensified antibiotic treatment on mortality and morbidity of TB meningitis in a phase 3 clinical trial, preceded with an explorative pharmacokinetic (PK) study to examine if higher oral doses rifampicin result in exposures similar to the i.v. dose used in our phase 2 trial, since oral rifampicin could be implemented much easier in low-resource settings.

Timeline

Start

2013-06

Primary completion

2013-10

Completion

2014-04

Publications

• Background Ruslami R, Ganiem AR, Dian S, Apriani L, Achmad TH, van der Ven AJ, Borm G, Aarnoutse RE, van Crevel R. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013 Jan;13(1):27-35. doi: 10.1016/S1473-3099(12)70264-5. Epub 2012 Oct 25.
• Background Marais S, Thwaites G, Schoeman JF, Torok ME, Misra UK, Prasad K, Donald PR, Wilkinson RJ, Marais BJ. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010 Nov;10(11):803-12. doi: 10.1016/S1473-3099(10)70138-9. Epub 2010 Sep 6.

Drugs

Indications