High-dose Rifampicin for the Treatment of Tuberculous Meningitis: a Dose-finding Study

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02169882
• Date of registration: 15/06/2014
• Prospective Registration: Yes
• Primary sponsor: Universitas Padjadjaran
• Public title: High-dose Rifampicin for the Treatment of Tuberculous Meningitis: a Dose-finding Study ReDEFINe
• Scientific 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
• Date of first enrolment: December 1, 2014
• Target sample size: 60
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02169882
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2/Phase 3

Countries of recruitment

Indonesia

Contacts

• Name: Rovina Ruslami, M.D., PhD
• Affiliation: Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or Female, aged 15 years or above.

2. Clinical suspicion of TBM and CSF/blood glucose ratio < 0.5.

3. None or less than 3 days of anti-tuberculosis chemotherapy taken for the current
infection.

4. Patient or representative (if the patient is incapacitated) is willing and able to
give informed consent for participation in the study.

5. Willingness to allow storage of specimens.

Exclusion Criteria:

Patients may not enter the study if any of the following apply:

1. Liver dysfunction (ALT > 5 times upper limit); kidney dysfunction (eGFR < 50 ml/min)

2. Pregnancy or breastfeeding (negative urine pregnancy test for all females of
child-bearing age).

3. Confirmed cryptococcus meningitis (LFA), or confirmed bacterial meningitis
(microscopy).

4. Rapid clinical deterioration at time of presentation (e.g. signs of sepsis, decreasing
consciousness or signs of cerebral oedema, or herniation)



Age minimum: 15 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Tuberculosis, Meningeal

Intervention(s)

Drug: Other TB drugs

Drug: Rifampicin

Drug: Placebo

Drug: Adjuvant dexamethasone

Primary Outcome(s)

Rifampicin concentrations in plasma and cerebrospinal fluid (CSF) [Time Frame: Day 2 (+/- 1) after administration of study drugs]

Secondary Outcome(s)

Resolution of blood and CSF inflammatory response [Time Frame: 7 days]

Grade 3 and 4 and serious adverse events [Time Frame: Within 60 days]

Mortality [Time Frame: 180 days]

Sensitivity of GeneXpert for diagnosing TBM [Time Frame: Within 6 weeks]

Neurological response [Time Frame: Within 60 days]

Neuroradiological response [Time Frame: 60 days]

Rifampicin concentrations in plasma and CSF at steady-state [Time Frame: Day 10 (+/- 1) after starting treatment with study drugs]

Secondary ID(s)

PGA-2000003601

TB-201406.01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

United States Agency for International Development (USAID)

Radboud University