Intensified Treatment Regimens for TB Meningitis: PK, PD and Tolerability Study

• Status: Completed
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, and is diagnosed in approximately 5-10% of TB patients. The incidence of TBM has increased considerably during the last decade, partly due to the HIV epidemic. Without treatment, virtually all patients with TB meningitis will die. With the current treatment regimens, TBM is fatal in approximately 30-50% of cases, and responsible for severe disability in a similar proportion of survivors.

Worldwide, Indonesia the third highest case load of tuberculosis with an estimated 500,000 new patients / year. Representative data are lacking, but it is clear that TBM is a growing problem. For instance, in Hasan Sadikin Hospital, the top-referral hospital for West Java Province (population 40 million), Indonesia, 40-50 cases of TBM were treated yearly in the late 90's compared to approximately 100 in recent years.

There is very little evidence for the current treatment regimen for TBM, which dates back to the late 60's. Therefore, there is an urgent need to evaluate intensified treatment of TBM in randomized trials. We hypothesize that higher dose rifampicin, moxifloxacin (possibly also at high dose), or both will improve outcome of TBM. To determine the experimental regimen(s) which should be compared with current regimen in phase 3 trials, we want to evaluate pharmacokinetic aspects and toxicity of candidate regimens in a phase 2 clinical trial in 60 patients with TBM in Indonesia.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Universitas Padjadjaran
• Collaborator: Radboud University
• Treatments: Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

Criteria

Inclusion Criteria:

• Tuberculous meningitis, diagnosed based on clinical and/or CSF criteria

• Age 15 years old or more

• Hospitalized for the treatment

Exclusion Criteria:

• Pregnancy/lactation

• On TB treatment within 7 days before inclusion

• Elevated liver enzyme (> 5x than normal values)

• Known hypersensitivity/intolerance to rifampicin or moxifloxacin

• Prolonged QTc interval in ECG or other detectable cardiac arrythmias, in the absence of hypokalemia

• Refusal to be included in the study