A Short Regimen for Rifampicin-resistant Isoniazid-susceptible TB

NCT06526039 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: N202404036
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess outcome of treatment and safety among patients with rifampicin-resistant isoniazid-susceptible pulmonary tuberculosis treated with a novel regimen consisting of isoniazid, bedaquiline, and moxifloxacin throughout for 6 months, supplemented by pyrazinamide for the initial 2 months.

Conditions

Tuberculosis, Pulmonary

Keywords

bedaquiline; isoniazid; moxifloxacin; tuberculosis; rifampicin resistance

Outcome Measures

Primary Outcomes (2)

• the proportion of patients with a favourable outcome at 12 months (53 weeks) post treatment initiation

  The primary efficacy outcome measure is the proportion of patients with a favourable outcome at 12 months (53 weeks) post treatment initiation

  12 months after treatment initiation

• the proportion of patients experiencing a grade 3 or greater adverse event during treatment and follow-up to 12 months (53 weeks) post treatment initiation.

  The primary safety outcome measure is the proportion of patients experiencing a grade 3 or greater adverse event, as defined by the CTCAE criteria except hyperuricemia which will be defined by the DAIDS criteria, during treatment and follow-up to 12 months (53 weeks) post treatment initiation.

  from treatment initiation to 12 months after treatment initiation

Secondary Outcomes (7)

• Sputum conversion

  through study completion, an average of 9 months

• Time to unfavourable efficacy outcome

  through study completion, an average of 9 months

• the proportion of patients with a favourable outcome at 24 months (105 weeks) post treatment initiation

  from treatment initiation to 24 months after treatment initiation

• mortality during treatment and follow-up

  from treatment initiation to 24 months after treatment initiation

• Change of regimen for adverse drug reactions

  through study completion, an average of 9 months

Study Arms (1)

Intervention

EXPERIMENTAL

Patients will be treated with a novel short regimen

Other: a novel short regimen

Interventions

a novel short regimen OTHER

An intensive phase consisting of isoniazid, bedaquiline, moxifloxacin and pyrazinamide for 2 months (9 weeks). A continuation phase consisting of isoniazid, bedaquiline, and levofloxacin for 4 months (17 weeks). Treatment may be extended for 3 months (13 weeks) in patients with severe disease or with delayed culture conversion, defined by culture positive at 4 months of treatment.

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A patient will be eligible for entry to the study if he/she:
• Is willing and able to give informed consent to be enrolled in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate)
• Is aged 18 years or older
• Has bacteriologically-confirmed pulmonary tuberculosis by Xpert MTB/RIF, other nucleic acid amplification test, or culture
• With initial laboratory result of resistance to rifampicin by Xpert MTB/RIF or Xpert MTB/RIF ultra, or other DST (line probe assay, culture); and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST. If rifampicin resistance is detected by Xpert MTB/RIF or Xpert MTB/RIF ultra in specimens with very low bacillary, rifampicin resistance has been confirmed by a repeat molecular test.
• With initial laboratory result of being susceptible to rifampicin by Xpert MTB/RIF or other DST (Xpert MTB/RIF ultra, line probe assay, culture) but are not able to tolerate rifampicin for whom rifabutin is intolerable or clinically not indicated; and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST
• With initial laboratory result of being susceptible to rifampicin by Xpert MTB/RIF or other DST (Xpert MTB/RIF ultra, line probe assay, culture) but rifamycin-sparing regimens are preferred due to drug-drug interaction, such as organ transplant recipients; and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST.
• With initial laboratory result that is susceptible to fluoroquinolone by Xpert MTB/XDR or other DST.
• If HIV test positive, is willing to be treated with ART in accordance with the national policies.
• Agrees to use effective barrier contraception or have an intrauterine contraceptive device during treatment phase if a pre-menopausal woman
• Has an identifiable address and expects to remain in the area for the duration of the study
• Is willing to adhere to the follow-up schedule and to study procedures

You may not qualify if:

• A patient will not be eligible for entry to the study if he/she:
• Is infected with a strain of M. Tuberculosis resistant to isoniazid by Xpert MTB/XDR or other tests
• Is infected with a strain of M. Tuberculosis resistant to fluoroquinolone by Xpert MTB/XDR or other tests
• Is infected with a strain of M. Tuberculosis resistant to amikacin by Xpert MTB/XDR or other tests and have no result of susceptibility of isoniazid by conventional drug susceptibility testing
• Has tuberculous meningitis or bone and joint tuberculosis
• Is critically ill, and in the judgment of the investigator, unlikely to survive more than 4 months.
• Is known to be pregnant or breast-feeding
• Is unable to attend or comply with treatment or follow-up schedule
• Is unable to take oral medication
• Has AST or ALT \>5 times the upper limit of normal
• Has AST or ALT \> 3 times the upper limit of normal ,and either with symptoms of hepatitis or bilirubin \> 1.5 times the upper limit of normal
• Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe.
• Is taking any medications contraindicated with the medicines in either the trial or control regimen
• Has a known allergy to any fluoroquinolone antibiotic
• Is currently taking part in another trial of a medicinal product

Sponsors & Collaborators

• Taipei Medical University WanFang Hospital: lead
• Hualien Tzu Chi General Hospital: collaborator
• Chest Hospital, Ministry of Health and Welfare, Taiwan: collaborator
• Chang-Hua Hospital: collaborator
• Taichung Veterans General Hospital: collaborator
• Taichung Hospital, Ministry of Health and Welfare: collaborator
• Taoyuan General Hospital: collaborator
• Kaohsiung Veterans General Hospital.: collaborator
• Kaohsiung Medical University Chung-Ho Memorial Hospital: collaborator

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Chen-Yuan Chiang, MD PhD MPH

CONTACT

+886229307930; cychiang@theunion.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice superintendent

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 29, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 29, 2024

Record last verified: 2024-07