NCT07227779

Brief Summary

This two-stage study will compare consented research participants with tuberculous meningitis receiving BPaLMZ to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), known as RHZE.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P75+ for phase_2

Timeline
51mo left

Started Jul 2026

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 11, 2025

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 13, 2025

Completed
9 months until next milestone

Study Start

First participant enrolled

July 28, 2026

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2028

Expected
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2030

Last Updated

July 30, 2026

Status Verified

July 1, 2026

Enrollment Period

1.7 years

First QC Date

November 11, 2025

Last Update Submit

July 28, 2026

Conditions

Tuberculous MeningitisHIVMeningitisTB - Tuberculosis

Outcome Measures

Primary Outcomes (2)

  • Time to Death

    24 Weeks

  • Hierarchical composite endpoint (survival + functional status)

    Hierarchical composite endpoint of survival and modified Rankin score (0-6 scale) assessed by Win Ratio

    24 Weeks

Secondary Outcomes (14)

  • Serious adverse events (SAE)

    28 weeks

  • Clinical Adverse Events

    28 weeks

  • Laboratory abnormalities

    28 weeks

  • Neuropathy

    28 weeks

  • Drug induced liver injury

    28 weeks

  • +9 more secondary outcomes

Study Arms (2)

BPaLMZ Regimen

EXPERIMENTAL

bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide (BPaLMZ)

Drug: BPaLMZ Regimen

Standard of Care Regimen

NO INTERVENTION

rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) therapy

Interventions

BPaLMZ RegimenDRUG

bedaquiline, pretomanid, linezolid, moxifloxacin, and pyrazinamide

BPaLMZ Regimen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • First Episode definite or probable TBM with physician intent to treat
  • Age ≥18 years
  • Provision of Informed Consent by participant or surrogate
  • Living with HIV
  • Weight \> 35kg, estimate or measured

You may not qualify if:

  • Additional active and confirmed CNS infection
  • Known rifampicin-resistant TB
  • Allergy or contraindication to a study medicine
  • More than 5 doses of any TB therapy received within the previous 14 days
  • Presence of jaundice, known liver cirrhosis, elevated ALT or AST \>3x ULN, or total bilirubin \>2x ULN
  • Estimated Glomerular Filtration Rate \<30 ml/min/1.73m2
  • Significant cardiac comorbidity, heart failure, arrhythmia, or QTc \>450 ms
  • Pregnancy or Breastfeeding
  • Cryptococcal antigen positivity in blood
  • Condition which makes participation not in the participant's best interest

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Infectious Diseases Institute

Kampala, Uganda

RECRUITING

Mbarara University of Science and Technology

Mbarara, Uganda

RECRUITING

MeSH Terms

Conditions

Tuberculosis, MeningealMeningitisLatent Tuberculosis

Condition Hierarchy (Ancestors)

Meningitis, BacterialCentral Nervous System Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsTuberculosis, Central Nervous SystemTuberculosis, ExtrapulmonaryTuberculosisMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsCentral Nervous System InfectionsCentral Nervous System DiseasesNervous System DiseasesNeuroinflammatory DiseasesLatent Infection

Study Officials

  • David Boulware, MD

    University of Minnesota

    PRINCIPAL INVESTIGATOR

Central Study Contacts

David Boulware, MD

CONTACT

612-624-9996coat.trial@gmail.com

Darlisha Williams, MPH

CONTACT

612-624-0469will1223@umn.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
McKnight Distinguished Professor

Study Record Dates

First Submitted

November 11, 2025

First Posted

November 13, 2025

Study Start

July 28, 2026

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

September 30, 2030

Last Updated

July 30, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will share

deidentified dataset

Shared Documents
STUDY PROTOCOL
Time Frame
At time of publication, as per ICJME
Access Criteria
public access
More information

Locations

UG(2)