Optimizing Treatment to Improve TBM Outcomes in Children (TBM-KIDS)
- Conditions
- Health Condition 1: null- Tuberculosis Meningitis in Children
- Registration Number
- CTRI/2017/03/008004
- Lead Sponsor
- Johns Hopkins University School of Medicine
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 27
1. Weight > 6kg
2. Age greater than or equal to 6 months to less than or equal to 12 years and, in the opinion of the investigator, can tolerate the treatment and study participation.
3. Probable or definite TBM according to diagnostic criteria (Appendix II) or a positive Gene Xpert CSF test.
4.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.
4. Participant can comply with the protocol requirements in the opinion of the site investigator.
1. TB treatment for more than 7 days within 30 days prior to enrollment
2. Exposure via close contact with someone with MDR-TB (or rifampicin mono-resistant TB) or personal history of MDR-TB (or rifampicin mono-resistant TB)
3. Known intolerance or allergy to any of the study drugs
4. Death imminent and expected within 24 hours, as assessed by the site investigator
5. Moderate to severe renal or liver dysfunction (Grade 2 or higher abnormalities of creatinine, ALT, or direct bilirubin)
6. 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)
7.Having participated in other clinical studies with investigational agents or treatments within 8 weeks prior to enrollment.
8.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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.Population plasma and CSF PK of rifampicin and levofloxacin: A population modelling approach will be used to describe pharmacokinetics of rifampicin and levofloxacin in plasma and CSF. This PK model will represent an immediate basis for linkage to the longitudinal efficacy measurements. <br/ ><br>2.Population PK/PD model assessing the relationship between PK of rifampicin and the primary efficacy endpoint, Modified Ranking Score (MRS) for children. <br/ ><br>3.Grade 3 or higher AEs during treatment phase <br/ ><br>Timepoint: 18 months <br/ ><br>
- Secondary Outcome Measures
Name Time Method 1.Overall longitudinal cognitive score and subscale (gross motor, visual reception, fine motor receptive language, expressive language) MSEL scoring system longitudinally, at baseline, 2, 12, and 18 months. <br/ ><br>2.Favorable TB treatment response at 48 weeks will be reported as a binary variable (favorable or unfavorable) at 48 weeks. <br/ ><br>Timepoint: 2,12,18 months