Tuberculosis
Conditions
Interventions
Rifampicin Isoniazid Linezolid Pyrazinamide Ethambutol
Rifampicin Isoniazid Pyrazinamide Ethambutol
Sponsors
National Institute of Allergy and Infectious Diseases
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Definite, probable, or possible TBM diagnosis wherein the participant is being committed to a full course of SOC anti-TB treatment for TBM in the setting of routine care. CSF, imaging, laboratory, and other results used to determine definite, probable, or possible TBM can be from testing performed as part of routine care, as long as obtained within 21 days prior to study entry 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, OR HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV-1 infection, or documentation of HIV diagnosis in the medical record by a healthcare provider 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 The following laboratory values obtained within 3 days prior to study entry: Serum creatinine =1.8 times upper limit of normal (ULN), Hemoglobin =8.0 g/dL for men, =7.5 g/dL for women Absolute neutrophil count =600/mm3, Platelet count =60,000/mm3, Alanine aminotransferase (ALT) =3 x ULN Total bilirubin =2 x ULN For participants of reproductive potential who have not been post-menopausal for at least 24 consecutive months (i.e., no menses within the preceding 24 months), or participants who have not undergone surgical sterilization, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation, documentation of a pregnancy while receivingstudy treatment and for 30 days after stopping study treatment
Exclusion criteria
Exclusion criteria: 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 For participants who are able to undergo the Brief Peripheral Neuropathy Screen (BPNS) within 21 days prior to study entry, Grade 3 subjective peripheral neuropathy score on the BPNS AND EITHER vibratory loss OR absent ankle jerks 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 (See protocol) For participants with HIV and ART-naïve, planned initiation of ART during the first 4 weeks after randomization For participants with HIV and on ART that includes a protease inhibitor, nevirapine, or other prohibited ART (see protocol), contraindication to switching to an acceptable alternative regimen (e.g., efavirenz, high-dose raltegravir or dolutegravir with nucleoside reverse transcriptase inhibitors, as per local SOC) prior to randomization. TB treatment, including study drugs, should be started as soon as possible 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Rankin Scale (6-death, 5-severe disability, 4-moderately severe disability, 3-moderate disability, 2-slight disability, 1-no significant disability, 0-no symptoms) at 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Modified Rankin Scale (all 7 levels) at 12, 24, 36, and 72 weeks Modified Rankin Scale using collapsed categories at 12, 24, 36, 48 and 72 weeks: mRS (0 or 1), (2 or 3), (4 or 5), (6) Modified Rankin Scale 5 or 6 at 12, 24, 36, 48 and 72 weeks Change in mRS from baseline to each of 12, 24, 36, 48, and 72 weeks Time to death over 48 and 72 weeks Proportion of participants with Grade 3 or higher AEs over 8 weeks Proportion of participants with a serious adverse event (SAE) over 8 weeks Proportion of participants who complete study treatments, which is defined as completing 168 doses within 185 days for Arm A and 252doses in 278 days for Arm B Proportion of participants with TBM IRIS (as defined in section 8.3) over 48 weeks Neurocognitive battery performance (e.g., Wechsler Adult Intelligence Scale Digit Symbol or Symbol Digit Modalities, Color Trails 1, Color Trails 2, Category Fluency, Hopkins Verbal Learning Test-Revised, Grooved Pegboard Bilateral, Finger-tapping Bilateral) at 24 and 48 weeks Patient Health Questionnaire (PHQ-9) total score and WHO DAS score at 24, 48, and 72 weeks Change in BMRC TBM grade at week 1. Time to coma clearance, which is defined as Glasgow Coma Score of 15 for =48 hours for hospitalized participants, over 4 weeks. Time to new neurological event, which is defined as fall in Glasgow Coma Score of =2 points for =48 hours for hospitalized participants or since last visit for non-hospitalized participa | — |
Countries
Kenya
Contacts
Public ContactCharles Kilel
KEMRI Walter Reed Project
Outcome results
None listed