The Safety and Efficacy of BDL(Bedaquiline Plus Delamanid Plus Linezolid) Regimen in Subjects With Pulmonary Infection of Multi-drug Resistant Tuberculosis (MDR-TB) or Rifampicin-Resistant Tuberculosis (RR-TB)

June 24, 2024 updated by: Beijing Chest Hospital

The goal of this investigator initiated trial (IIT) is to learn if a 6-9months BDL regimen (bedaquiline plus delamanid plus linezolid）works to treat adults with multi-drug resistant tuberculosis or rifampicin-resistant pulmonary tuberculosis, in the context of Pretomanid not available in China. It will also learn about the safety of BDL regimen.

The main questions it aims to answer are:

  1. What is the percentage of participants with favorable treatment outcome at the end of treatment?
  2. What are the frequency and degree of AE and SAE associated with BDL regimen?

Participants will take Bedaquiline +Delamanid+ Linezolid for 6 months, option for 9 months for subjects who remain culture positive at month 4 to 6. Safety and efficacy data will be monitored and collected during treatment. A 12 month follow-up will be conducted after treatment completion.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230000
        • Not yet recruiting
        • Anhui Chest Hospital
        • Principal Investigator:
          • Hua Wang
        • Contact:
    • Beijing
      • Beijing, Beijing, China, 101149
        • Recruiting
        • Beijing Chest Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Mengqiu Gao, doctor
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Not yet recruiting
        • Wuhan Institute for Tuberculosis Control
        • Contact:
          • Juan Du
        • Principal Investigator:
          • Juan Du
    • Hunan
      • Changsha, Hunan, China, 410000
        • Not yet recruiting
        • Changsha Central Hospital
        • Contact:
        • Principal Investigator:
          • Yi Pei
      • Changsha, Hunan, China, 410000
        • Not yet recruiting
        • Hunan Chest Hospital
        • Contact:
        • Principal Investigator:
          • Zhongheng Yi
    • Shandong
      • Jinan, Shandong, China, 250000
        • Not yet recruiting
        • Shandong Public Health Clinical Center
        • Contact:
        • Principal Investigator:
          • Yu Xiong
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • Not yet recruiting
        • Public Health Clinical Meadical Center of Chengdu
        • Contact:
        • Principal Investigator:
          • Guihui Wu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • 1.A patient with multi-drug resistant/rifampicin-resistant pulmonary tuberculosis (MDR/RR-TB) with recent laboratory evidence (culture or molecular testing) within the last two months
  • 2.Age 18 years above
  • 3.No prior use of neither bedaquiline, delamanid, linezolid, or use for less than 4 weeks
  • 4.Positive culture result for mycobacterial at baseline(regardless smear positive or negative). No anti-tuberculosis treatment received within one month.
  • 5.For patients who don't have baseline sputum culture results,positive sputum smear and no effective anti-tuberculosis treatment administered
  • 6. No history of respiratory failure or heart failure, and no clinically significant manifestations of arrhythmia, with a QTcF under 450ms
  • 7.Promise to adhere to the treatment and follow-up schedule, complete treatment monitoring, and promptly report adverse reactions to the responsible physician
  • 8.Voluntarily participate in this study and sign the informed consent form

Exclusion Criteria

  • 1.According to DMID, peripheral neuropathy is classified as grade 3 or 4. Alternatively, participants with grade 1 or 2 neuropathy, which the investigator believes may progress/worsen during the study
  • 2.Elevation of ALT or AST ≥3 times the upper limit of normal, or elevation of total bilirubin and direct bilirubin ≥2 times the upper limit of normal
  • 3.Pregnant women or those who intent to pregnant during treatment
  • 4.Participants who have participated in other drug trials in the past three months
  • 5.Known congenital QT interval prolongation or any disease prolonging the QT interval, or QTc>450 ms
  • 6.History of symptomatic arrhythmias or clinically relevant bradycardia
  • 7.Any cardiac disease that could precipitate arrhythmias, such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive heart failure with decreased left ventricular ejection fraction
  • 8.History of known, untreated, persistent hypothyroidism
  • 9.Electrolyte disturbances, especially hypokalemia, hypocalcemia, or hypomagnesemia
  • 10.History of allergy or known allergic reactions to any investigational drug or related substances
  • 11.BMI<17 kg/m2
  • 12.Karnofsky performance score under 50, or as determined by the principal investigator, the anticipated survival of the participant is not expected to exceed 6 months
  • 13.Participants expected to require surgical intervention following assessment of their pulmonary disease

Withdrawal Criteria

  1. Serious adverse events caused by the intervention
  2. Confirmed QTcF interval ≥ 500ms or clinically significant ventricular arrhythmias
  3. The expert panel deems the continuation of this combination regimen inappropriate
  4. The patient requests withdrawal

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BDL interventionv group
Drug: BDL regimen

Drug:bedaquiline 100mg tablets

Other Names:

Bdq TMC-207 bedaquiline 400 mg once daily for 2 weeks then 200mg 3 times per week

Drug:delamanid 50mg tablets

Other Names:

Dlm OPC-67683 delamanid 100mg 2 times daily

Drug:linezolid Scored 600mg tablets

Other Names:

Lzd linezolid 600mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The efficacy outcome at the end of treatment
Time Frame: Baseline (within 9 days before treatment initiation), weeks 1, 2, 4, 6, 8 of treatment, thereafter every 4 weeks until week 26(or 39 weeks for patients require prolonged treatment) during the intervention
The efficacy outcome of treatment: bacteriological positive patients completed the prescribed treatment course, demonstrating bacteriological response without evidence of treatment failure Notes: bacteriological outcome response:bacterial culture conversion to negative and no recurrence of positivity thereafter Bacteriological conversion refers to confirmed tuberculosis patients having two or more consecutive negative sputum culture results, with at least a 7-day interval between each Recurrence of positivity refers to two or more consecutive sputum cultures were positive after bacteriological conversion, with at least a 7-day interval between each
Baseline (within 9 days before treatment initiation), weeks 1, 2, 4, 6, 8 of treatment, thereafter every 4 weeks until week 26(or 39 weeks for patients require prolonged treatment) during the intervention
Frequency of any adverse events (AEs) and serious adverse events (SAEs) occurring during the treatment period
Time Frame: Baseline (within 9 days before treatment initiation), weeks 1-16, 20 and 26 during the intervention
Baseline (within 9 days before treatment initiation), weeks 1-16, 20 and 26 during the intervention

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of patients have bacterial recurrence within 12 months after treatment completion
Time Frame: 3,6,9,12 months after the intervention
3,6,9,12 months after the intervention
Time for sputum culture conversion to stable negativity during treatment
Time Frame: 3,6,9,12 months after the intervention
3,6,9,12 months after the intervention
Proportion of patients who discontinued treatment due to adverse reactions or permanently unable to take the medication
Time Frame: during the intervention
during the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Chest Hospital

Collaborators

Anhui Chest Hospital
Changsha Central Hospital
Wuhan Institute for Tuberculosis Control
Shandong Public Health Clinical Center
Public Health Clinical Medical Center of Chengdu
Hunan Chest Hospital

Investigators

  • Principal Investigator: Yuhong Liu, Ph.D, Beijing Chest Hostal
  • Principal Investigator: Mengqiu Gao, Ph.D, Beijing Chest Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

June 14, 2024

First Submitted That Met QC Criteria

June 24, 2024

First Posted (Actual)

June 26, 2024

Study Record Updates

Last Update Posted (Actual)

June 26, 2024

Last Update Submitted That Met QC Criteria

June 24, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YNLX-2024-009

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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