Trial of a Six-Month Regimen of High-Dose Rifampicin, High-Dose Isoniazid, Linezolid, and Pyrazinamide Versus a Standard Nine-Month Regimen for the Treatment of Adults and Adolescents With Tuberculous Meningitis
- Conditions
- Tuberculous Meningitis
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 330
Inclusion Criteria:<br><br> - Definite, probable, or possible TBM diagnosis wherein the participant is being<br> committed to a full course of SOC anti-TB treatment for TBM in the setting of<br> routine care. CSF, imaging, laboratory, and other results used to determine<br> definite, probable, or possible TBM can be from testing performed as part of routine<br> care, as long as obtained within 21 days prior to study entry<br><br> - Persons aged =15 years<br><br> - Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1<br> enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 30 days prior to<br> study entry, OR<br><br> - HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit<br> at any time prior to entry and confirmed by a licensed Western blot or a second<br> antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1<br> antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000<br> copies/mL are also acceptable as documentation of HIV-1 infection, or documentation<br> of HIV diagnosis in the medical record by a healthcare provider<br><br> - Documentation within 3 days prior to study entry of stage of disease using BMRC TBM<br> grade:<br><br> - Grade I: Glasgow Coma Score 15, no focal neurological deficits<br><br> - Grade II: Glasgow Coma Score 11-14 or 15 with focal neurological deficits<br><br> - Grade III: Glasgow Coma Score =10<br><br> - The following laboratory values obtained within 3 days prior to study entry:<br><br> - Serum creatinine =1.8 times upper limit of normal (ULN)<br><br> - Hemoglobin =8.0 g/dL for men, =7.5 g/dL for women<br><br> - Absolute neutrophil count =600/mm3<br><br> - Platelet count =60,000/mm3<br><br> - Alanine aminotransferase (ALT) =3 x ULN<br><br> - Total bilirubin =2 x ULN<br><br> - For participants of reproductive potential who have not been post-menopausal for at<br> least 24 consecutive months (i.e., no menses within the preceding 24 months), or<br> participants who have not undergone surgical sterilization, hysterectomy, bilateral<br> salpingectomy, bilateral oophorectomy, or tubal ligation, documentation of a serum<br> or urine pregnancy test result (positive or negative; see protocol for test<br> sensitivity requirement) within 21 days prior to study entry<br><br> - Participants with documentation of a positive pregnancy test will be consented using<br> the consent form for pregnant participants.<br><br>Participants of reproductive potential with documentation of a negative pregnancy test<br>must agree to use at least one acceptable form of contraception, or abstain from sexual<br>activity that could lead to pregnancy while receiving study treatment and for 30 days<br>after stopping study treatment.<br><br>Participants who are not of reproductive potential or whose partner(s) has documented<br>azoospermia are not required to use contraception. Any statement of self-reported<br>sterility or that of the partner's must be entered in the source documents<br><br> - Ability and willingness of participant or parent or legally authorized<br> representative (for adolescents or participants unable to provide consent) to<br> provide informed consent/assent<br><br> - Ability to comply with the protocol requirements in the opinion of the site<br> investigator<br><br>Exclusion Criteria:<br><br> - More than 14 cumulative days of first-line TB medications, including but not limited<br> to INH, RIF, EMB, and PZA, received within 90 days prior to study entry<br><br> - Known current or previous drug resistant TB infection (i.e., resistance to one or<br> more first-line TB medications, including but not limited to INH, RIF, EMB, LZD and<br> PZA)<br><br> - Known allergy/sensitivity or any hypersensitivity to components of study TB drugs<br> (INH, RIF, LZD, PZA, and EMB) or their formulation<br><br> - For participants who are able to undergo the Brief Peripheral Neuropathy Screen<br> (BPNS) within 21 days prior to study entry, Grade 3 subjective peripheral neuropathy<br> score on the BPNS AND EITHER vibratory loss OR absent ankle jerks<br><br> - Expected concomitant use or use up to 21 days prior to study entry of monoamine<br> oxidase inhibitors or selective serotonin reuptake inhibitors, or concomitant use of<br> any other drug with significant interaction with the study drugs (See protocol)<br><br> - For participants with HIV and ART-naïve, planned initiation of ART during the first<br> 4 weeks after randomization<br><br> - For participants with HIV and on ART that includes a protease inhibitor, nevirapine,<br> or other prohibited ART (see protocol), contraindication to switching to an<br> acceptable alternative regimen (e.g., efavirenz, high-dose raltegravir or<br> dolutegravir with nucleoside reverse transcriptase inhibitors, as per local SOC)<br> prior to randomization. TB treatment, including study drugs, should be started as<br> soon as possible<br><br> - Contraindication to LP at discretion of treating clinician (e.g., unequal pressures<br> between intracranial compartments due to mass lesion, non-communicating<br> hydrocephalus)<br><br> - Positive cryptococcal antigen, gram stain, bacterial culture, or other test result<br> obtained from a CSF specimen collected within 21 days prior to entry as part of<br> routine care indicating CNS infection with a pathogen other than Mtb (e.g.,<br> cryptococcal meningitis, bacterial meningitis).
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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)
- Secondary Outcome Measures
Name Time Method