Short-Course Regimen With Bedaquiline, Moxifloxacin and Pyrazinamide for Early Bactericidal Activity in Drug-Susceptible Tuberculosis

Summary

\# Brief Summary

This study aims to evaluate the early bactericidal activity (EBA), safety, and tolerability of 4-month short-course regimens containing bedaquiline, moxifloxacin, and pyrazinamide in patients with drug-susceptible tuberculosis. This is a prospective, randomized, controlled, multicenter study planned to enroll 45 rifampicin-susceptible tuberculosis patients, who will be randomized in a 1:1:1 ratio to the BZMD group (bedaquiline + pyrazinamide + moxifloxacin + delamanid), BZMH group (bedaquiline + pyrazinamide + moxifloxacin + isoniazid), and standard control group. Subjects in the test groups will receive 17 weeks (4 months) of group-specific treatment regimens, while subjects in the control group will receive 26 weeks (6 months) of standard HRZE regimen treatment.

The primary endpoint is the change from baseline in log₁₀ colony-forming units (CFU) per milliliter of sputum specimen from Day 0 (pre-dose) to Day 14 of treatment (EBA CFU₀-₁₄), used to evaluate the early bactericidal activity of the drugs. Secondary endpoints include EBA CFU and EBA TTP (time to positive culture) at other time intervals, pharmacokinetic characteristics, sustained microbiological clearance rates, relapse rates, and safety indicators. The study will analyze the daily decline in log₁₀ CFU counts and daily increase in TTP using nonlinear mixed-effects models to reflect the bactericidal activity of the study regimens.

This study will help provide more effective and safer short-course treatment options for Chinese patients with drug-susceptible tuberculosis, thereby improving treatment adherence and treatment success rates, and providing scientific evidence for optimizing short-course treatment regimens for drug-susceptible tuberculosis.

Conditions

• Tuberculosis, Pulmonary
• Drug-Susceptible Pulmonary Tuberculosis

Interventions

DRUG

Bedaquiline (B)

Bedaquiline tablets administered orally. Dosing: 400 mg once daily for the first 2 weeks, then 200 mg three times per week for weeks 3-17. Used in both experimental arms (BZMD and BZMH groups) as part of the 4-month short-course regimen for drug-susceptible tuberculosis treatment.

DRUG

Moxifloxacin

Moxifloxacin 400 mg tablets administered orally once daily before or after meals throughout the entire treatment period (17 weeks). Used in both experimental arms (BZMD and BZMH groups) as part of the 4-month short-course regimen for drug-susceptible tuberculosis treatment.

DRUG

Pyrazinamide (PZA)

Pyrazinamide tablets administered orally once daily in the morning during intensive phase (8 weeks). Dosing by weight: 1000 mg for 40.0-49.9 kg, 1500 mg for 50.0-70.9 kg, 2000 mg for ≥75.0 kg. Used in both experimental arms (BZMD and BZMH groups) and control group as part of tuberculosis treatment regimen.

DRUG

Delamanid (D)

Delamanid tablets administered orally at 100 mg twice daily (total daily dose 200 mg) throughout the entire treatment period (17 weeks). Used only in the BZMD experimental arm as part of the 4-month short-course regimen for drug-susceptible tuberculosis treatment.

DRUG

Isoniazid (H)

Isoniazid tablets administered orally at 300 mg once daily in the morning throughout the entire treatment period. Used in the BZMH experimental arm (17 weeks) and in the standard control group (26 weeks) as part of tuberculosis treatment regimens.

DRUG

Rifampicin (R)

Rifampicin tablets administered orally once daily in the morning throughout the entire treatment period (26 weeks). Dosing by weight: 450 mg for 40.0-49.9 kg, 600 mg for 50.0-70.9 kg and ≥75.0 kg. Used only in the standard control group as part of the 6-month standard tuberculosis treatment regimen.

DRUG

Ethambutol (E)

Ethambutol tablets administered orally during the intensive phase (8 weeks). Dosing by weight: 750 mg for 40.0-49.9 kg, 1000 mg for 50.0-70.9 kg and ≥75.0 kg. Used only in the standard control group as part of the 6-month standard tuberculosis treatment regimen.

Sponsors & Collaborators

• Huashan Hospital

  collaborator OTHER

• Guangzhou National Laboratory

  collaborator UNKNOWN

• Shanghai Pulmonary Hospital, Shanghai, China

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-08-20

Primary Completion

2026-12-31

Completion

2027-12-31