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)

Beijing Chest Hospital

Status and phase: Enrolling; Phase 4

Conditions: Pulmonary Tuberculosis

Treatments: Drug: BDL regimen

Study type: Interventional

Funder types: Other

Identifiers

NCT06476210

YNLX-2024-009

Details and patient eligibility

About

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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

BDL interventionv group

Experimental group

Treatment:

Drug: BDL regimen