Clinical trial NCT06476210: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pulmonary Tuberculosis
Lead sponsor: Beijing Chest Hospital
Sponsor class: OTHER
Collaborators: name: Public Health Clinical Medical Center of Chengdu
name: Wuhan Institute for Tuberculosis Control
name: Changsha Central Hospital
name: Anhui Chest Hospital
name: Hunan Chest Hospital
name: Shandong Public Health Clinical Center
First posted: 2024-06-26
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: The efficacy outcome at the end of treatment
timeFrame: 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
measure: Frequency of any adverse events (AEs) and serious adverse events (SAEs) occurring during the treatment period
timeFrame: Baseline (within 9 days before treatment initiation), weeks 1-16, 20 and 26 during the intervention
Secondary outcomes:
measure: Incidence of patients have bacterial recurrence within 12 months after treatment completion
timeFrame: 3,6,9,12 months after the intervention
measure: Time for sputum culture conversion to stable negativity during treatment
timeFrame: 3,6,9,12 months after the intervention
measure: Proportion of patients who discontinued treatment due to adverse reactions or permanently unable to take the medication
timeFrame: during the intervention
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Chest Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Chest Hospital
state: Beijing
city: Wuhan
country: China
facility: Wuhan Institute for Tuberculosis Control
state: Hubei
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Chest Hospital
state: Hunan
city: Jinan
country: China
facility: Shandong Public Health Clinical Center
state: Shandong
city: Chengdu
country: China
facility: Public Health Clinical Meadical Center of Chengdu
state: Sichuan
Study officials:
affiliation: Beijing Chest Hostal
name: Yuhong Liu, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chest Hospital
name: Mengqiu Gao, Ph.D
role: PRINCIPAL_INVESTIGATOR
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