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PARTNERSHIPS FOR ENHANCED ENGAGEMENT IN RESEARCH (PEER) HEALTH
Cycle 1

High-­dose Rifampicin for the Treatment of Tuberculous Meningitis: a Dose-­‐Finding Study (ReDEFINe: Rifampicin DosE FINding Study)
 
Principal Investigator: Rovina Ruslami, Universitas Padjadjaran
NIH-Supported Collaborator: H. Clifford Lane, NIH intramural researcher 
Title of NIH Award: INA-RESPOND (Indonesian Research Partnership in Infectious Disease)

Project Overview
Background: 
TB meningitis (TBM) is the most severe manifestation of TB, 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. 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 III trial can be performed.

Objectives: 
The overall aim is to establish the optimal dose of rifampicin for TBM, which can be evaluated in a follow-­‐up multicenter phase III RCT. The primary objective is to generate pharmacokinetic (PK) data for higher doses of rifampcin patients with TBM. 

Methods:
This will be a double-blinded, 1:1:1 randomized, placebo controlled, phase IIb trial. Roughly 60 adult TBM patients will be randomized to one of three arms consisting of varying doses of rifampicin administered orally, as part of a standard 4 drug regimen for TBM. Pharmacokinetics data, safety/tolerability and efficacy data will be collected. Subjects will be followed for 180 days.

Public Health Impact: 
Finding the right dose of rifampcin could alter the standard of care and reduce mortality and morbidity of this important, and difficult to treat, disease.

NIH Collaborator:
Dr. Lane is an established investigator in the study of the immunopathogenesis and treatment of HIV infection. He is also the US Project Leader for the recently established INdonesiA-RESearch Partnership On iNfectious Disease (INA-RESPOND) clinical research network and is responsible for overseeing the NIH funding that is combined with resources from the Indonesian NIHRD, Universities and Hospitals to support clinical research in infectious diseases under the umbrella of INA-RESPOND.