Pulmonary Tuberculosis
Conditions
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.
Interventions
DRUGBDL 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
Sponsors
Public Health Clinical Medical Center of Chengdu
Wuhan Institute for Tuberculosis Control
Changsha Central Hospital
Anhui Chest Hospital
Hunan Chest Hospital
Shandong Public Health Clinical Center
Beijing Chest Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The efficacy outcome at the end of treatment | 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 |
| Frequency of any adverse events (AEs) and serious adverse events (SAEs) occurring during the treatment period | Baseline (within 9 days before treatment initiation), weeks 1-16, 20 and 26 during the intervention | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of patients have bacterial recurrence within 12 months after treatment completion | 3,6,9,12 months after the intervention |
| Time for sputum culture conversion to stable negativity during treatment | 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 | during the intervention |
Countries
China
Contacts
Primary ContactYuhong Liu, Ph.D
Backup ContactWei Shu, Master
Outcome results
None listed