Safety and effectiveness of a 6-month all-oral treatment regimen for the treatment of rifampicin-resistant tuberculosis in Vietnam

Stage IV pragmatic randomized clinical trial to compare 6 month all oral BPaLLf (bedaquiline, pretomanid, linezolid and levofloxacin) regimen with WHO-recommended BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) regimen in term of safety and effectiveness for the treatment of rifampicin-resistant tuberculosis in Vietnam

Status

Recruiting

Phases

Phase 4

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN18086293

Enrollment

400

Registered

2024-07-01

Start date

2024-03-01

Completion date

Unknown

Last updated

2024-07-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Treatment of fluoroquinolones susceptible rifampicin-resistant TB patients Infections and Infestations

Interventions

In Vietnam, a pragmatic randomized clinical trial will be conducted to compare two standardized rifampicin-resistant TB (RR-TB) regimens: BPaL-M with BPaL-Lf (levofloxacin replaces moxifloxacin in the

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Diagnosed with pulmonary TB by a microbiological test (molecular or phenotypic), and has laboratory-confirmed resistance to at least rifampicin by either molecular or phenotypic drug susceptibility test 2. Fluoroquinolone resistance excluded either on phenotypic or genotypic DST 3. Aged 15 years or above, regardless of HIV status, at the time of enrolment 4. Willing and able to give informed consent to be enrolled in the trial and adhere to the trial procedures and follow-up schedule (signed or witnessed consent if illiterate)

Exclusion criteria

Exclusion criteria: 1. Known allergies, hypersensitivity, or intolerance to any of the BPaL-M/Lf component drugs 2. Pregnant or breast-feeding 3. Liver enzymes >3 times the upper limit of normal (AST or ALT) 4. Taking any medications contraindicated with the medicines in the trial 5. QTcF > 450ms 6. Peripheral neuropathy of Grade 3–4 7. Any baseline biochemical laboratory value consistent with Grade 4 toxicity 8. Has DST showing infection with a strain resistant to any of the study regimens’ component drugs (Bdq, Pa, Lzd, Mfx or Lfx) or delamanid (Dlm) 9. Has been previously exposed to any of the BPaL-M/Lf drugs (Bdq, Pa, Lzd, Mfx or Lfx) or Dlm for more than four weeks, unless DST confirms susceptibility to these drugs 10. The clinical DR-TB committee decides that it is not in the best interest of the patient to be enrolled on the BPaL-M/Lfx due to the necessity of an individualized TB treatment regimen

Design outcomes

Primary

Measure	Time frame
QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation (difference between baseline QTcF interval and highest value during treatment for the QTcF interval) measured using electrocardiogram (ECG) at baseline, 2 weeks after treatment starts and monthly until treatment completes	—

Secondary

Measure	Time frame
1. Compare safety between BPaL-M and BPaL-Lf 1.1. QT interval corrected for heart rate using Fridericia's formula (QTcF) > 500 ms during treatment measured using ECG is at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.2. QTcF increase = 60ms from baseline measured using ECG at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.3. Any TB treatment change due to adverse event (AE) measured using linezolid's dose change, linezolid's temporary interruption, linezolid's permanent interruption, temporary or permanent interruption of full regimen due to adverse events at any time during treatment 1.4. Treatment failure due to AEs measured using permanent interruption of full regimen due to adverse events at any time during treatment 1.5. Max grade of QT-prolongation and its timing measured using ECG at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.6. Max grade of peripheral neuropathy and its timing measured using clinical screening of symptoms, and brief peripheral neuropathy screening (BPNS) at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.7. Max grade of myelosuppression and its timing measured using full blood count at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.8. Max grade of optic neuritis and its timing measured using vision and color acuity testing at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.9. Max grade of hepatotoxicity and its timing measured using liver enzymes assessed at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.10. Any grade 3-4 AE measured using clinical assessment, blood tests, BPNS, vision and color acuity testing at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.11. Any serious adverse event (SAE) measured using clinical assessment, blood tests, BPNS, vision	—

Measure

Time frame

1. Compare safety between BPaL-M and BPaL-Lf 1.1. QT interval corrected for heart rate using Fridericia's formula (QTcF) > 500 ms during treatment measured using ECG is at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.2. QTcF increase = 60ms from baseline measured using ECG at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.3. Any TB treatment change due to adverse event (AE) measured using linezolid's dose change, linezolid's temporary interruption, linezolid's permanent interruption, temporary or permanent interruption of full regimen due to adverse events at any time during treatment 1.4. Treatment failure due to AEs measured using permanent interruption of full regimen due to adverse events at any time during treatment 1.5. Max grade of QT-prolongation and its timing measured using ECG at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.6. Max grade of peripheral neuropathy and its timing measured using clinical screening of symptoms, and brief peripheral neuropathy screening (BPNS) at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.7. Max grade of myelosuppression and its timing measured using full blood count at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.8. Max grade of optic neuritis and its timing measured using vision and color acuity testing at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.9. Max grade of hepatotoxicity and its timing measured using liver enzymes assessed at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.10. Any grade 3-4 AE measured using clinical assessment, blood tests, BPNS, vision and color acuity testing at baseline, 2 weeks after treatment starts, and monthly until the end of treatment 1.11. Any serious adverse event (SAE) measured using clinical assessment, blood tests, BPNS, vision

—

Countries

Viet Nam

Contacts

Public ContactThi Mai Phuong Nguyen

phuong.nguyen@ugent.be+84949357999

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026