Optimizing Treatment to Improve TBM Outcomes in Children

• Status: Completed
• Trial end date: 2020-11-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University
• Collaborators: B. J. Medical College, Pune; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute for Research in Tuberculosis, Chennai, India; University of North Carolina
• Treatments: Ethambutol; Levofloxacin; Ofloxacin; Rifampin

Criteria

Inclusion Criteria:

• Weight > 6kg

• Age ≥ 6 months to < 12 years and, in the opinion of the investigator, can tolerate the treatment and study participation.

• Probable or definite TBM according to diagnostic criteria or a positive Gene Xpert cerebrospinal fluid (CSF) test.

• Since participants will all be under legal age of independent consent, a parent or legal guardian must be willing and able to provide informed consent. If the subject is of appropriate age, she/he will also be asked to give assent if developmentally appropriate and clinically possible.

• Participant can comply with the protocol requirements in the opinion of the site investigator.

Exclusion Criteria:

• TB treatment for > 7 days

• Exposure via close contact with someone with multi drug resistant TB (MDR-TB) (or rifampicin mono-resistant TB) or personal history of MDR-TB (or rifampicin mono-resistant TB)

• Known intolerance or allergy to any of the study drugs

• Death imminent and expected within 24 hours, as assessed by the site investigator

• Moderate to severe renal or liver dysfunction (Grade 2 or higher abnormalities of creatinine, alanine aminotransferase (ALT), or direct bilirubin)

• HIV infection with any of the following:

Planned initiation of antiretroviral treatment (ART) during the experimental treatment phase (first 8 weeks), as initiation of ART is contraindicated in that time period with TBM.

On ART with planned continued use of a protease inhibitor or nevirapine (children can be switched to an acceptable alternative regimen and then participate)

• Having participated in other clinical studies with investigational agents or treatments within 8 weeks prior to enrollment.

• A clinically significant active medical condition or the presence of any concomitant severe illness or rapidly deteriorating health condition (outside of TB), which, in the opinion of the site investigator, would prevent appropriate participation in the trial, or that would make implementation of the protocol or interpretation of the study results difficult, or otherwise make the subject a poor candidate for a clinical trial.