A Study on the Short-course Treatment Regimen Containing Pretomanid for Drug-resistant Tuberculosis

NCT07126639 | Not Yet Recruiting DMC

• 1 other identifier: Wuhan Pulmonary H
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Rifampicin-resistant tuberculosis (RR-TB) is characterized by a long treatment course, high incidence of adverse reactions, low cure rate and high recurrence rate. This is related to the large number of drugs in the RR-TB treatment regimen, high incidence of adverse reactions and long treatment course, which leads to poor patient compliance. There is an urgent need for new, effective and safe short-course regimens for drug-resistant tuberculosis. A 6-month short-course oral regimen containing pretomanid was introduced in 2020. However, as pretomanid is not yet available in China, it has not been verified and promoted in China. Pretomanid is expected to be launched in China in 2025, and it is urgent to evaluate the application of the new short-course regimen containing pretomanid in the Chinese population. This study is a prospective, randomized, controlled clinical trial. It plans to include RR-TB patients aged ≥12 years in multiple domestic centers. Under the guidance of rapid molecular drug susceptibility test results, the experimental group will be treated with bedaquiline, pretomanid, linezolid and moxifloxacin for 6 months, while the control group will be treated with bedaquiline, delamanid, linezolid and levofloxacin or bedaquiline, delamanid, linezolid and clofazimine for 6 months, depending on the susceptibility to fluoroquinolones. For patients with unknown susceptibility to fluoroquinolones, bedaquiline, delamanid, linezolid, levofloxacin and clofazimine will be used for 6 months. The efficacy and safety will be evaluated to provide a basis for the introduction and implementation of new short-course regimens for RR-TB in China.

Conditions

Efficacy and Safety

Keywords

BPaLM; short-course treatment regiment

Outcome Measures

Primary Outcomes (1)

• Favorable outcomes during the treatment period

  Cure: Completing 80% or more of the medication dosage as required by the protocol within 28 weeks after the start of the research treatment, with no evidence of treatment failure, and the Mycobacterium tuberculosis (MTB) cultures of the last two sputum specimens (collection interval ≥ 14 days) at the end of treatment being negative. Treatment completion: Completing more than 80% of the medication dosage as required by the protocol within 28 weeks after the start of the research treatment, with no evidence of treatment failure, but without evidence that the MTB cultures of two sputum specimens collected at an interval of at least 14 days are negative.

  From the initiation of treatment until the 28th week.

Secondary Outcomes (3)

• Favorable outcomes during the follow - up period after treatment

  From the beginning of the treatment until 72 weeks.

• Favorable outcomes with an extended follow - up period

  Follow - up was conducted until 108 weeks after enrollment.

• Unfavorable outcome

  From the time of enrollment until the 108th week of follow - up

Study Arms (2)

test group

EXPERIMENTAL

A six - month regimen containing bedaquiline (BDQ), pretomanid (Pa), linezolid (LZD), and moxifloxacin (MFX)

Drug: bedaquiline; Drug: Pretomanid (Pa); Drug: linezolid; Drug: Moxifloxacin (M)

Control group (Group A)

ACTIVE COMPARATOR

The control group was stratified according to the drug susceptibility results of fluoroquinolones (FQs). The FQs - sensitive group was treated with the BDLL regimen (bedaquiline (BDQ), delamanid (DLM), linezolid (LZD), and levofloxacin (LFX)), the FQs - resistant group was treated with the BDLC regimen (BDQ, DLM, LZD, and clofazimine (CFZ)), and the group with unknown drug susceptibility was treated with the BDLLfxC regimen (BDQ, DLM, LZD, LFX, and CFZ). The duration of all regimens was 6 months.

Drug: bedaquiline; Drug: linezolid; Drug: Delamanid (D); Drug: Levofloxacin; Drug: clofazimine

Interventions

bedaquiline DRUG

Administer 400 mg orally once daily for the first two weeks, followed by 200 mg orally three times a week for the subsequent 22 weeks.

Control group (Group A); test group

Pretomanid (Pa) DRUG

Administer 200 mg orally once daily for six months.

test group

linezolid DRUG

Administer 600 mg orally once daily for six months.

Control group (Group A); test group

Moxifloxacin (M) DRUG

Administer 400 mg orally once daily for six months.

test group

Delamanid (D) DRUG

Administer 100 mg orally twice daily for six months.

Control group (Group A)

Levofloxacin DRUG

Administer 800 mg orally once daily for six months.

Control group (Group A)

clofazimine DRUG

Administer 100 mg orally once daily for six months.

Control group (Group A)

Eligibility Criteria

• Age: 12 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• he research participants themselves voluntarily signed the informed consent form before being enrolled; for those without full capacity for civil conduct, the consent form was signed by their legal guardians.
• The research participants (and their guardians) indicated their willingness to complete all steps and intervention periods of the study.
• Male or female, aged 12 years or older, weighing 30 kilograms or more. Confirmed cases of pulmonary tuberculosis pathogen, with molecular or phenotypic drug sensitivity results within the past 3 months confirming resistance to rifampicin, and confirmed by the pathogen culture results of sputum collected at the time of enrollment.
• Fertile women not in pregnancy, voluntarily undergoing pregnancy tests, with negative results, and willing to use highly effective contraceptive measures from the time of signing the informed consent until 3 months after the end of the study treatment.
• For fertile men, use condoms or other methods to ensure effective contraception for their sexual partners.
• Women in lactation, willing to stop breastfeeding from the time of signing the informed consent until 3 months after the end of the study treatment.
• Voluntary to undergo HIV testing. If the result is positive, voluntarily accept antiretroviral therapy.

You may not qualify if:

• Had a known hypersensitivity reaction to any drug in the protocol. Was participating in any clinical trial of other drugs. At the screening stage, had cardiovascular disease risk: QTcF interval over 480 milliseconds; within 60 days before enrollment, had a history of clinically significant arrhythmia that the investigator considered could be clinically significant, and the investigator considered that participating in the study might increase the risk; decompensated heart failure; grade 3 hypertension and not reaching the control target; thyroid dysfunction; abnormal serum calcium, magnesium or potassium levels.
• Had a history of optic nerve or peripheral nerve lesion, and the investigator considered that it might progress/deteriorate during the study or was not suitable for participating in this study.
• At the screening stage, had the following liver disease manifestations: active viral hepatitis; decompensated stage of liver cirrhosis.
• At the screening stage, had the following kidney disease history or kidney-related manifestations: unstable or rapidly progressive kidney disease history; moderate/severe renal function impairment or end-stage renal disease; male serum creatinine ≥ 133 μmol/L, female serum creatinine ≥ 124 μmol/L.
• Other laboratory test abnormalities: hemoglobin level \< 8.0 g/dL; platelet count \< 75,000/mm³; absolute neutrophil count \< 1000/mm³; aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 3×ULN; total bilirubin \> 2×ULN, or \> 1.5×ULN, combined with other liver enzyme abnormalities; albumin \< 30 g/L.
• The investigator considered that the study participants could not complete the study process, or participating in the study was unsafe for the study participants.

Sponsors & Collaborators

• Wuhan Pulmonary Hospital: lead

MeSH Terms

Interventions

bedaquiline; pretomanid; Linezolid; Moxifloxacin; OPC-67683; Fumigant 93; Levofloxacin; Clofazimine

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ofloxacin; Phenazines; Heterocyclic Compounds, 3-Ring

Study Officials

• Shuang Wei, M.D.

  Wuhan Pulmonary Hospital

  STUDY DIRECTOR

Central Study Contacts

Shuang Wei, Doctor, director of hospital

CONTACT

+8602783602347; shuangwei@tjh.tjmu.edu.cn

Juan Du, doctor

CONTACT

8615327334680; dudu1109@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Wuhan Pulmonary hospital

Study Record Dates

• First Submitted: July 13, 2025
• First Posted: August 17, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: August 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE