A5384: Open lable study to compare a 6-month regimen of high-dose of anti TB medicationsagainst 9 month standard of care (SOC) regimen for the treatment of tuberculous meningitis(TBM)
- Conditions
- Health Condition 1: G01- Meningitis in bacterial diseases classified elsewhere
- Registration Number
- CTRI/2023/05/053012
- Lead Sponsor
- IH DAIDS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
Persons aged >=15 years
Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 30 days prior to study entry
Documentation within 3 days prior to study entry of stage of disease using BMRC TBM grade:
Grade I: Glasgow Coma Score 15, no focal neurological deficits
Grade II: Glasgow Coma Score 11-14 or 15 with focal neurological deficits
Grade III: Glasgow Coma Score <=10
Participants with documentation of a positive pregnancy test will be consented using the consent form for pregnant participants
Ability and willingness of participant or parent or legally authorized representative (for adolescents or participants unable to provide consent) to provide informed consent/assent
Ability to comply with the protocol requirements in the opinion of the site investigator
More than 14 cumulative days of first-line TB medications, including but not limited to INH, RIF, EMB, and PZA, received within 90 days prior to study entry
Known current or previous drug resistant TB infection (i.e., resistance to one or more first-line TB medications, including but not limited to INH, RIF, EMB, LZD and PZA)
Known allergy/sensitivity or any hypersensitivity to components of study TB drugs (INH, RIF, LZD, PZA, and EMB) or their formulation
Expected concomitant use or use up to 21 days prior to study entry of monoamine oxidase inhibitors or selective serotonin reuptake inhibitors, or concomitant use of any other drug with significant interaction with the study drugs
For participants with HIV and ART-naïve, planned initiation of ART during the first 4 weeks after randomization
Contraindication to LP at discretion of treating clinician (e.g., unequal pressures between intracranial compartments due to mass lesion, non-communicating hydrocephalus)
Positive cryptococcal antigen, gram stain, bacterial culture, or other test result obtained from a CSF specimen collected within 21 days prior to entry as part of routine care indicating CNS infection with a pathogen other than Mtb (e.g., cryptococcal meningitis, bacterial meningitis).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves functional outcomes measured by the modified Rankin Scale (mRS) when compared with WHO SOC for the treatment of TBM.Timepoint: 48 weeks
- Secondary Outcome Measures
Name Time Method 1 Modified Rankin Scale (all 7 levels) <br/ ><br>2 Change in mRS from baseline to each of 12, 24, 36, 48, and 72 weeks <br/ ><br>3 Proportion of participants who complete study treatments, which is defined as completing 168 doses within 185 days for Arm A and 252 doses in 278 days for Arm B <br/ ><br>4 Proportion of participants with TBM IRIS (as defined in protocol) over 48 weeks <br/ ><br>5 Wechsler Adult Intelligence Scale Digit Symbol or Symbol Digit Modalities <br/ ><br>6 Time to coma clearance, which is defined as Glasgow Coma Score of 15 for â?¥48 hours for hospitalized participants, over 4 weeks <br/ ><br>Timepoint: 1 TF: Time Frame: At weeks 12,24,36 and 72 <br/ ><br>2 TF: At 12, 24, 36, 48, and 72 weeks <br/ ><br>3 TF : At day 185 and day 278 <br/ ><br>4 TF : At week 48 <br/ ><br>5 TF : At week 24 and 48 <br/ ><br>6 TF: At week 4 <br/ ><br>