BPaL(M) Regimen for the Treatment of MDR/RR-TB

NCT ID: NCT05381194

Last Updated: 2024-03-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-13

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Multidrug- and Rifampicin-resistant Tuberculosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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single arm (investigational arm)

BPaLM

Group Type EXPERIMENTAL

BPaL(M) regimen

Intervention Type DRUG

Patients diagnosed with MDR/RR-TB are initially assigned to the BPaLM regimen as a single-arm for treatment initiation. Afterward, if MDR/RR-TB is confirmed to be fluoroquinolone-resistant by molecular or phenotypic DST, the treatment is switched to the BPaL regimen (for 24 weeks). On the other hand, if MDR/RR-TB is confirmed to be fluoroquinolone-susceptible, treatment for MDR/RR-TB is maintained with the BPaLM regimen (for 26 weeks).

The dosage of each medication is as follows:

* Bedaquiline 400mg/day for the 2 weeks, 200mg/TIW afterward
* Pretomanid 200mg/day
* Linezolid 600mg/day for the 9weeks, 300mg/day afterward
* Moxifloxacin 400mg/day

Interventions

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BPaL(M) regimen

Patients diagnosed with MDR/RR-TB are initially assigned to the BPaLM regimen as a single-arm for treatment initiation. Afterward, if MDR/RR-TB is confirmed to be fluoroquinolone-resistant by molecular or phenotypic DST, the treatment is switched to the BPaL regimen (for 24 weeks). On the other hand, if MDR/RR-TB is confirmed to be fluoroquinolone-susceptible, treatment for MDR/RR-TB is maintained with the BPaLM regimen (for 26 weeks).

The dosage of each medication is as follows:

* Bedaquiline 400mg/day for the 2 weeks, 200mg/TIW afterward
* Pretomanid 200mg/day
* Linezolid 600mg/day for the 9weeks, 300mg/day afterward
* Moxifloxacin 400mg/day

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pusan National University Hospital

OTHER

Sponsor Role collaborator

Samsung Medical Center

OTHER

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role collaborator

Severance Hospital

OTHER

Sponsor Role collaborator

Chonnam National University Hospital

OTHER

Sponsor Role collaborator

The Catholic University of Korea

OTHER

Sponsor Role collaborator

Chungbuk National University Hospital

OTHER

Sponsor Role collaborator

Ulsan University Hospital

OTHER

Sponsor Role collaborator

Soon Chun Hyang University

OTHER

Sponsor Role collaborator

Incheon St.Mary's Hospital

OTHER

Sponsor Role collaborator

DongGuk University

OTHER

Sponsor Role collaborator

National Medical Center, Seoul

OTHER

Sponsor Role collaborator

Asan Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Tae Sun Shim

Clinical professor, MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Asan Medical Center

Seoul, Songpa-gu, South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Tae Sun Shim, MD, PhD

Role: CONTACT

+82-2-3010-3892

Facility Contacts

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Tae Sun Shim, MD, PhD

Role: primary

+82-2-3010-3892

Other Identifiers

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BPaL(M)

Identifier Type: -

Identifier Source: org_study_id

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