NCT02958709

Optimizing Treatment to Improve TBM Outcomes in Children

Phase I/II Randomized, Open-label Trial to Evaluate the PK, Safety, and Outcomes of Treatment Including High Dose Rifampicin +/- Levofloxacin vs Standard Treatment for Pediatric Tuberculous Meningitis (TBM)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 6 Months – 12 Years
• Healthy volunteers: Not accepted

Summary

In this open-labeled, randomized clinical trial, the Investigator will assess the safety and pharmacokinetics (PK) of model-optimized doses of rifampicin (RIF) with or without levofloxacin (LEVO) given to children as part of multidrug treatment for tuberculous meningitis (TBM) versus standard treatment. The Investigators will also assess functional and neurocognitive outcomes by treatment group, as measured by the Pediatric Modified Rankin Score (MRS) and the Mullen Scales of Early Learning (MSEL), respectively.

Detailed description

Open-label, randomized clinical trial in three treatment groups. Patients with probable or definite TB meningitis (TBM) will all receive isoniazid and pyrazinamide at standard doses for 8 weeks. Arm 1 participants will receive high-dose rifampicin plus ethambutol (EMB) at standard doses for 8 weeks. Arm 2 participants will receive high-dose rifampicin plus levofloxacin for 8 weeks. Arm 3 participants will receive rifampicin plus ethambutol at standard doses for 8 weeks (control arm). Patients will be screened to confirm TBM diagnosis, will receive 8 weeks of study treatment, and then will receive isoniazid (INH)/rifampicin for an additional 40 weeks, to complete 12 months of TBM treatment. All participants will receive oral steroids. PK sampling will be performed within first week and 6 (+/- 2) weeks following treatment initiation. Participants will have scheduled follow-up visits to assess safety and clinical status. In addition, functional and neurocognitive outcomes up to 18 months following treatment initiation will be assessed. Interim PK and safety analyses will be performed to ensure dosing is producing predefined PK targets and safety is acceptable. It is anticipated that a majority of children will be hospitalized for the initial 2-8 weeks of the study.

Conditions

• Tuberculosis, Meningeal

Interventions

Type	Name	Description
DRUG	High-dose: RIF, INH, PZA, EMB	high-dose rifampicin plus standard dose H,Z,E, given for 8 weeks in treatment Arms 1 and 2
DRUG	High dose: RIF, INH, PZA, LEVO	high-dose rifampicin plus standard dose H,Z, with levofloxacin substituted for ethambutol for 8 weeks in treatment Arm 2
DRUG	Standard of care: RIF, INH, PZA, EMB	standard doses of R,H,Z,E given for 8 weeks in treatment Arm 3, control arm.

Timeline

• Start date: 2017-02-22
• Primary completion: 2020-11-15
• Completion: 2020-11-15
• First posted: 2016-11-08
• Last updated: 2021-10-28

Locations

3 sites across 2 countries: India, Malawi