Short-course Regimens for the Treatment of Pulmonary Tuberculosis

Summary

The purpose of this study is to determine whether one or two 17-week regimens of tuberculosis treatment bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ) plus either Rifabutin (Rb) or Delamanid (D or DLM) are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week.

The first 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus rifabutin (Rb) (BMZRB) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and Rifabutin (Rb) (2 BMZRb/2 BMRb, Arm 1)

The Second 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus delamanid (D or DLM); (BMZD) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and delamanid (D or DLM) (2 BMZD/2 BMD, Arm 2)

The standard 26-week treatment control regimen which is two months of isoniazid, rifampin, ethambutol, and pyrazinamide (2HRZE) followed by four months of isoniazid and rifampin (4HR); (2HRZE/4HR, Arm 3)

Target enrollment is 288 male and female participants (96/arm). participants. Participants will be followed until 78 weeks post-randomization, or until the last enrolled participant completes 52 weeks post-randomization, whichever comes first.

Conditions

• Tuberculosis, Pulmonary
• Tuberculosis Infection

Interventions

DRUG

Rifabutin

Rifabutin (Rb) is added to the bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) regimen for first 8 weeks and continued for next 9 weeks with bedaquiline (B or BDQ) and moxifloxacin (M)

DRUG

Delamanid

Delamanid (D or DLM) is added to the bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) regimen for first 8 weeks and continued for next 9 weeks with bedaquiline (B or BDQ) and moxifloxacin (M)

DRUG

Bedaquiline

Bedaquiline is part of interventional arms with bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ).

DRUG

Moxifloxacin

Moxifloxacin is part of interventional arms with bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ).

DRUG

Pyrazinamide

Pyrazinamide is part of interventional arms with bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ). Pyrazinamide is part of control regimen (HRZE).

DRUG

Isoniazid

Isoniazid is part of control regimen (HRZE).

DRUG

Rifampin

Rifampin is part of control regimen (HRZE).

DRUG

Ethambutol

Ethambutol is part of control regimen (HRZE).

Sponsors & Collaborators

• Tuberculosis Trials Consortium

  collaborator NETWORK

• Centers for Disease Control and Prevention

  lead FED

Principal Investigators

• Kelly Dooley, MD · Johns Hopkins University

• Daniel W Fitzgerald, MD · Weill Medical College of Cornell University

• Ekaterina V Kurbatova, MD, PhD, MPH · Centers for Disease Control and Prevention

• Wendy Carr, PhD · Centers for Disease Control and Prevention

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-21

Primary Completion

2026-12-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States
• Canada
• Haiti
• South Africa
• Uganda
• Vietnam

Study Locations