Clinical trial NCT05381194: BPaL(M) Regimen for the Treatment of MDR/RR-TB
Official title: The 6-month BPaL(M) Regimen for the Treatment of Patients With MDR/RR-TB: Multicenter, Single-arm, Operational Research, Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Multidrug- and Rifampicin-resistant Tuberculosis
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Pusan National University Hospital
name: Samsung Medical Center
name: Seoul National University Hospital
name: Severance Hospital
name: Chonnam National University Hospital
name: The Catholic University of Korea
name: Chungbuk National University Hospital
name: Ulsan University Hospital
name: Soon Chun Hyang University
name: Incheon St.Mary's Hospital
name: DongGuk University
name: National Medical Center, Seoul
First posted: 2022-05-19
Enrollment: 80
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to analyze the efficacy of a new regimen using Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin for 24 weeks or Bedaquiline, Pretomanid, Linezolid for 26 weeks for the treatment of MDR/RR-TB through the clinical trial.

Detailed description: The BPaL (Bedaquiline, Pretomanid, Linezolid) regimen has been proven effective for the treatment of Fluoroquinolone-resistant MDR-TB through studies such as the NixTB and ZeNix trials. In addition, the BPaLM regimen has been demonstrated to have excellent efficacy in RR-TB patients through the TB-PRACTECAL study. This study aims to analyze the efficacy of the BPaL(M) regimen in Korean MDR/RR-TB patients.

Eligibility criteria: Inclusion Criteria:

1. At least 19 years old at enrolment
2. Bodyweight over 35Kg
3. If rifampicin resistance is confirmed through molecular or phenotypic drug susceptibility testing conducted on sputum or bronchoscopy specimens within 3 months of screening
4. Chest radiological findings consistent with pulmonary tuberculosis

Exclusion Criteria:

1. Uncontrolled DM
2. Extrapulmonary TB that would require treatment longer than would be usual for pulmonary TB
3. Less than 30 Karnofsky score at enrolment
4. BMI less than 17
5. Known severe allergy to any of the BPaLM regimen drugs
6. Medical history of Glucose-galactose malabsorption, galactose intolerance, and Lapp lactase deficiency
7. HIV-positive
8. The QTcF interval exceeds 450 msec on the electrocardiogram at baseline
9. Patients who are at risk of Torsade de Pointes due to underlying heart diseases such as heart failure or arrhythmia
10. For women of childbearing potential if the pregnancy test is positive, women who are breastfeeding or planning to become pregnant within 6 months of discontinuation/termination of treatment during the study, or who do not want contraception (i.e., oral and subcutaneous hormonal contraceptives, condoms, diaphragms, intrauterine device, or use of appropriate contraceptive methods including abstinence)

    \*Note: Double contraception (e.g., when a male uses a barrier contraceptive method such as a condom, a female partner uses a hormonal contraceptive or an additional contraceptive method such as an intrauterine device) is required while taking the study drug and up to 6 months after stopping/terminating the study drug. In particular, taking the study drug may affect the efficacy of hormonal contraceptives, and even if you are using only barrier contraception at the same time with your partner, you cannot be sure of preventing pregnancy, so it is necessary to maintain double contraception.
11. Men who plan to become pregnant during the study period or within 6 months of discontinuation/termination of treatment, or who do not wish to use double contraception or abstinence during this period.
12. Patients who have Grade 3 or 4 or higher peripheral neuritis, or Grade 1 or 2 with a high probability of progression to peripheral neuritis,
13. Current use of monoamine oxidase Inhibitor or used 2 weeks before treatment
14. Use of serotonergic antidepressant within 3 days of treatment
15. Any contraindication that may affect QTc interval (amiodarone, chloroquine, chlorpromazine, clarithromycin, haloperidol, etc.)
16. Any contraindication that may cause myelosuppression
17. Taking drugs that affect the cytochrome P450 enzyme within 30 days (quinidine, tyramine, ketoconazole, fluconazole, testosterone, quinine, gestodene, metyrapone, phenelzine, doxorubicin, troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline, cimetidine, dextromethorphan, etc.)
18. Previously treated with Bedaquiline or Linezolid for more than 4 weeks
19. Abnormal value of a blood test at baseline:

    * Hypokalemia, Hemoglobin \< 8.0 g/dL, Platelet \< 75,000/mm3, ANC \< 1000/mm3
    * AST or ALT \> 3 X ULN, Total bilirubin \>2.0 X ULN, Albumin \< 3.2 mg/dL
    * Serum creatinine \> 2 X ULN, Serum calcium \< LLN, Serum magnesium \< LLN

Primary outcomes:
measure: A microbiological failure or clinical failure or relapse
timeFrame: until 12 months after the end of treatment
Secondary outcomes:
measure: Time to sputum culture conversion during the treatment period
timeFrame: 26 weeks or 24 weeks
measure: Proportion of culture-negative patients at specific times (weeks 4, 8, 12, 16, and 24 or 26)
timeFrame: 26 weeks or 24 weeks
measure: Prescribed dose of Linezolid
timeFrame: 26 weeks or 24 weeks
measure: All-cause mortality
timeFrame: 26 weeks or 24 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
Study officials:
References: