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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

Primary Purpose

Tuberculous Meningitis

Status
Not yet recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rifampicin (RIF)
Isoniazid (INH)
Linezolid (LZD)
Pyrazinamide (PZA)
ethambutol (EMB)
Rifampicin
Isoniazid
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculous Meningitis focused on measuring Tuberculosis, meningeal, Tuberculosis, CNS Disease

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 serum or urine pregnancy test result (positive or negative; see protocol for test sensitivity requirement) within 21 days prior to study entry
  • Participants with documentation of a positive pregnancy test will be consented using the consent form for pregnant participants.

Participants of reproductive potential with documentation of a negative pregnancy test must agree to use at least one acceptable form of contraception, or abstain from sexual activity that could lead to pregnancy while receiving study treatment and for 30 days after stopping study treatment.

Participants who are not of reproductive potential or whose partner(s) has documented azoospermia are not required to use contraception. Any statement of self-reported sterility or that of the partner's must be entered in the source documents

  • 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

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).

Sites / Locations

  • Hospital Nossa Senhora da Conceicao CRS
  • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
  • Byramjee Jeejeebhoy Government Medical College (BJMC) CRS
  • Moi University Clinical Research Center (MUCRC) CRS
  • Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
  • Malawi CRS
  • Nutrición-Mexico CRS
  • Barranco CRS
  • Durban International CRS
  • Milton Park CRS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

RIF 35 mg/kg + INH 15 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 2 weeks, followed by RIF 35 mg/kg + INH 10 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 6 weeks, and then RIF 35 mg/kg and INH 10 mg/kg for 16 weeks, for a total of 24 weeks of study treatment.

WHO SOC: RIF 10 mg/kg + INH 5 mg/kg + ethambutol (EMB) 20 mg/kg + PZA 25 mg/kg for 8 weeks, followed by RIF 10 mg/kg and INH 5 mg/kg for 28 weeks, for a total of 36 weeks of study treatment. Up to 15 mg/kg or a maximum of 900 mg daily of oral RIF will be permitted in this arm at clinician's discretion.

Outcomes

Primary Outcome Measures

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

Modified Rankin Scale (all 7 levels)
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
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 252 doses in 278 days for Arm B
Proportion of participants with TBM IRIS (as defined in protocol) over 48 weeks
Wechsler Adult Intelligence Scale Digit Symbol or Symbol Digit Modalities
Neurocognitive battery performance
Color Trails 1, 2
Neurocognitive battery performance
Category Fluency
Neurocognitive battery performance
Hopkins Verbal Learning Test-Revised
Neurocognitive battery performance
Grooved Pegboard Bilateral
Neurocognitive battery performance
Finger-tapping Bilateral
Neurocognitive battery performance
Patient Health Questionnaire (PHQ-9) total score
defined as Glasgow Coma Score of 15 for ≥48 hours for hospitalized participants over 4 weeks
WHO DAS score
defined as Glasgow Coma Score of 15 for ≥48 hours for hospitalized participants over 4 weeks
Change in BMRC TBM grade at week 1. BMRC TBM grade is defined as:
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
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 participants, new onset seizures, new focal neurologic deficit
CSF to plasma ratio
Rate of CSF uptake
Plasma absorption rate constant (ka)
Drug clearance (Cl/F)
Volume of distribution (Vd)
Post-hoc Bayesian predictions of secondary parameters Cmax
Time to Cmax
Time to AUC0-24
Time to plasma elimination half-life
Time to CSF elimination half-life

Full Information

First Posted
April 8, 2022
Last Updated
August 8, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT05383742
Brief Title
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
Official Title
A Phase II, Randomized, Open-Label 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: Improved Management With Antimicrobial AGents Isoniazid rifampiciN LinEzolid for TBM (IMAGINE-TBM)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 31, 2023 (Anticipated)
Primary Completion Date
August 2, 2026 (Anticipated)
Study Completion Date
August 2, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to compare a 6-month regimen of high-dose rifampicin (RIF), high-dose isoniazid (INH), linezolid (LZD), and pyrazinamide (PZA) versus the World Health Organization (WHO) standard of care (SOC) treatment for tuberculosis meningitis (TBM).
Detailed Description
Rationale: TBM is a devastating illness with high risk of mortality and severe neurologic morbidity. Although recent data suggest that significant dose increases in RIF may improve outcomes in TBM, mortality remains high, and enhanced treatment strategies are needed. In addition, limited data are available to guide treatment duration in adults with TBM. The overall goal of this Phase II, randomized, open-label trial is to assess the PK, safety, and longitudinal treatment outcomes of an optimized 6-month regimen of high-dose RIF, high-dose INH, LZD, and PZA to the WHO 9-month SOC regimen for the treatment of TBM. Primary objective: To determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves functional outcomes measured by the modified Rankin Scale (mRS) at 48 weeks compared with WHO SOC for the treatment of TBM. Design: Participants with definite, probable, or possible TBM will be randomized to one of the two study arms below and randomization will be stratified by HIV status and stage of disease as defined by the modified BMRC criteria. Arm A: RIF 35 mg/kg + INH 15 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 2 weeks, followed by RIF 35 mg/kg + INH 10 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 6 weeks, and then RIF 35 mg/kg and INH 10 mg/kg for 16 weeks, for a total of 24 weeks of study treatment. Arm B: WHO SOC: RIF 10 mg/kg + INH 5 mg/kg + EMB 20 mg/kg + PZA 25 mg/kg for 8 weeks, followed by RIF 10 mg/kg and INH 5 mg/kg for 28 weeks, for a total of 36 weeks of study treatment. Up to 15 mg/kg or a maximum of 900 mg daily of oral RIF will be permitted in this arm at clinician's discretion. All participants in Arms A and B will receive pyridoxine, while receiving INH, and adjunctive corticosteroids according to disease severity for at least 6 weeks. All participants in Arms A and B will be followed from randomization to week 72. Procedures: Study visits will include interval history, blood collection for laboratory testing, peripheral neuropathy screening, visual acuity, color vision, and contrast sensitivity visual testing to monitor for AEs. Lumbar puncture will be performed for assessments of CSF microbiology, LAM and other biomarkers. Optional collection and storage of blood and storage of remaining CSF for future testing will occur. Urine will be obtained for LAM assessment. Plasma and CSF PK assessments will be performed. Participants will undergo assessment of functional status with the mRS and WHO DAS 2.0. Participants will also be assessed with a neurocognitive battery and depression questionnaire (PHQ-9).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculous Meningitis
Keywords
Tuberculosis, meningeal, Tuberculosis, CNS Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
330 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
RIF 35 mg/kg + INH 15 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 2 weeks, followed by RIF 35 mg/kg + INH 10 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 6 weeks, and then RIF 35 mg/kg and INH 10 mg/kg for 16 weeks, for a total of 24 weeks of study treatment.
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
WHO SOC: RIF 10 mg/kg + INH 5 mg/kg + ethambutol (EMB) 20 mg/kg + PZA 25 mg/kg for 8 weeks, followed by RIF 10 mg/kg and INH 5 mg/kg for 28 weeks, for a total of 36 weeks of study treatment. Up to 15 mg/kg or a maximum of 900 mg daily of oral RIF will be permitted in this arm at clinician's discretion.
Intervention Type
Drug
Intervention Name(s)
Rifampicin (RIF)
Intervention Description
Rifampicin 35 mg/kg
Intervention Type
Drug
Intervention Name(s)
Isoniazid (INH)
Intervention Description
Isoniazid 10 or15 mg/kg
Intervention Type
Drug
Intervention Name(s)
Linezolid (LZD)
Intervention Description
1200 mg
Intervention Type
Drug
Intervention Name(s)
Pyrazinamide (PZA)
Intervention Description
25 mg/kg
Intervention Type
Drug
Intervention Name(s)
ethambutol (EMB)
Intervention Description
20 mg/kg
Intervention Type
Drug
Intervention Name(s)
Rifampicin
Intervention Description
10 mg/kg
Intervention Type
Drug
Intervention Name(s)
Isoniazid
Intervention Description
5 mg/kg
Primary Outcome Measure Information:
Title
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)
Time Frame
At 48 Weeks
Secondary Outcome Measure Information:
Title
Modified Rankin Scale (all 7 levels)
Time Frame
At weeks 12,24,36 and 72
Title
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)
Time Frame
12, 24, 36, 48 and 72 weeks
Title
Modified Rankin Scale 5 or 6
Time Frame
At 12, 24, 36, 48 and 72 weeks
Title
Change in mRS from baseline to each of 12, 24, 36, 48, and 72 weeks
Time Frame
At 12, 24, 36, 48, and 72 weeks
Title
Time to death over 48 and 72 weeks
Time Frame
At weeks 48 and 72
Title
Proportion of participants with Grade 3 or higher AEs over 8 weeks
Time Frame
At 8 weeks
Title
Proportion of participants with a serious adverse event (SAE) over 8 weeks
Time Frame
At 8 weeks
Title
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
Time Frame
At day 185 and day 278
Title
Proportion of participants with TBM IRIS (as defined in protocol) over 48 weeks
Time Frame
At week 48
Title
Wechsler Adult Intelligence Scale Digit Symbol or Symbol Digit Modalities
Description
Neurocognitive battery performance
Time Frame
At week 24 and 48
Title
Color Trails 1, 2
Description
Neurocognitive battery performance
Time Frame
At week 24 and 48
Title
Category Fluency
Description
Neurocognitive battery performance
Time Frame
At week 24 and 48
Title
Hopkins Verbal Learning Test-Revised
Description
Neurocognitive battery performance
Time Frame
At week 24 and 48
Title
Grooved Pegboard Bilateral
Description
Neurocognitive battery performance
Time Frame
At week 24 and 48
Title
Finger-tapping Bilateral
Description
Neurocognitive battery performance
Time Frame
At week 24 and 48
Title
Patient Health Questionnaire (PHQ-9) total score
Description
defined as Glasgow Coma Score of 15 for ≥48 hours for hospitalized participants over 4 weeks
Time Frame
At 24, 48, and 72 weeks
Title
WHO DAS score
Description
defined as Glasgow Coma Score of 15 for ≥48 hours for hospitalized participants over 4 weeks
Time Frame
At 24, 48, and 72 weeks
Title
Change in BMRC TBM grade at week 1. BMRC TBM grade is defined as:
Description
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
Time Frame
At week 1
Title
Time to coma clearance, which is defined as Glasgow Coma Score of 15 for ≥48 hours for hospitalized participants, over 4 weeks.
Time Frame
At week 4
Title
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 participants, new onset seizures, new focal neurologic deficit
Time Frame
At week 48
Title
CSF to plasma ratio
Time Frame
At Day 3, Week 2, 6 or 8
Title
Rate of CSF uptake
Time Frame
At Day 3, Week 2, 6 or 8
Title
Plasma absorption rate constant (ka)
Time Frame
At Day 3, Week 2, 6 or 8
Title
Drug clearance (Cl/F)
Time Frame
At Day 3, Week 2, 6 or 8
Title
Volume of distribution (Vd)
Time Frame
At Day 3, Week 2, 6 or 8
Title
Post-hoc Bayesian predictions of secondary parameters Cmax
Time Frame
At Day 3, Week 2, 6 or 8
Title
Time to Cmax
Time Frame
At Day 3, Week 2, 6 or 8
Title
Time to AUC0-24
Time Frame
At Day 3, Week 2, 6 or 8
Title
Time to plasma elimination half-life
Time Frame
At Day 3, Week 2, 6 or 8
Title
Time to CSF elimination half-life
Time Frame
At Day 3, Week 2, 6 or 8
Other Pre-specified Outcome Measures:
Title
Proportion of participants who relapsed by 12 and 24 weeks after completion of study treatments
Time Frame
At week 12 and 24
Title
Positive or negative CSF Xpert Ultra
Time Frame
At Day 3, week 2 and week 8
Title
Positive or negative CSF and urine LAM
Time Frame
At Day 3, weeks 2, 8 and 12
Title
Change in sterilization of CSF culture
Time Frame
At Weeks 2 and 6-8
Title
Change in CSF white blood cell count
Time Frame
At Weeks 2 and 6-8
Title
Change in CSF glucose
Time Frame
At Weeks 2 and 6-8
Title
Change in CSF blood glucose ratio
Time Frame
At Weeks 2 and 6-8
Title
Change in CSF protein
Time Frame
At Weeks 2 and 6-8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility 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 serum or urine pregnancy test result (positive or negative; see protocol for test sensitivity requirement) within 21 days prior to study entry Participants with documentation of a positive pregnancy test will be consented using the consent form for pregnant participants. Participants of reproductive potential with documentation of a negative pregnancy test must agree to use at least one acceptable form of contraception, or abstain from sexual activity that could lead to pregnancy while receiving study treatment and for 30 days after stopping study treatment. Participants who are not of reproductive potential or whose partner(s) has documented azoospermia are not required to use contraception. Any statement of self-reported sterility or that of the partner's must be entered in the source documents 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 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ACTG Clinicaltrials.gov Coordinator
Phone
(301) 628-3348
Email
ACTGCT.gov@fstrf.org
Facility Information:
Facility Name
Hospital Nossa Senhora da Conceicao CRS
City
Porto Alegre
ZIP/Postal Code
91350-200
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rita Lira, MD
Phone
+55 51-33572603
Email
lrita@ghc.com.br
Facility Name
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
City
Rio De Janeiro
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brenda Hoagland, MD
Phone
55 21 38659122
Email
E-mbrenda.hoagland@ipec.fiocruz.br
Facility Name
Byramjee Jeejeebhoy Government Medical College (BJMC) CRS
City
Pune
ZIP/Postal Code
411001
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nishi Suryavanshi, MD
Phone
91-20-26052419
Email
nishi@jhumitpune.com
Facility Name
Moi University Clinical Research Center (MUCRC) CRS
City
Eldoret
ZIP/Postal Code
30100
Country
Kenya
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Viola Kirui
Phone
254-711-729856
Email
viola.kirui@gmail.com
Facility Name
Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
City
Kericho
Country
Kenya
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samwel Chirchir
Phone
254-52-2030686
Email
samwel.chirchir@usamru-k.org
Facility Name
Malawi CRS
City
Lilongwe
Country
Malawi
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thokozani Makuhunga
Phone
265-175-5056
Email
E-mtmakuhunga@unclilongwe.org
Facility Name
Nutrición-Mexico CRS
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brenda Crabtree-Ramirez, MD
Phone
52-5555130010
Email
brenda.crabtree@infecto.mx
Facility Name
Barranco CRS
City
Lima
ZIP/Postal Code
4
Country
Peru
Facility Contact:
First Name & Middle Initial & Last Name & Degree
María Caballero, MD
Phone
+51 206-7800
Email
mestrella@impactaperu.org
Facility Name
Durban International CRS
City
Durban
ZIP/Postal Code
4091
Country
South Africa
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rosie Mngqibisa, MD
Phone
27-31-2611093
Email
mngqibisa@ecarefoundation.com
Facility Name
Milton Park CRS
City
Harare
Country
Zimbabwe
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pamela Marimbe-Mukwekwerere, MD
Phone
+263-242-257066
Email
pmukwekwerere@uz-ctrc.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie results in the publication, after deidentification
IPD Sharing Time Frame
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH
IPD Sharing Access Criteria
With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data

Learn more about this trial

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

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