NCT05081401

Innovating(IN) Shorter(S), All- Oral, Precised(P), Individualized(I) Treatment Regimen(RE) for Rifampicin Resistant Tuberculosis(INSPIRE-TB)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,050 (estimated)
• Sponsor: Huashan Hospital · Academic / Other
• Sex: All
• Age: 16 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The INSPIRE-TB study is a pragmatic, multicentre, randomised, controlled, non-inferiority open-label trial to evaluate the efficacy and safety of seven 9-month oral regimens compared to a 9-month standard of care (SOC) regimen in RR-TB participants susceptible to fluoroquinolones, and a bedaquiline-containing 9-month oral regimen compared to a 20-month conventional regimen in RR-TB participants resistant to fluoroquinolones

Detailed description

RR-TB patients susceptible to fluoroquinolones are identified with the Xpert MTB/XDR assay (Cepheid; Sunnyvale, CA, USA). Experimental arms are seven oral regimens with a five-drug combination of the following: bedaquiline, linezolid, a fluoroquinolone (moxifloxacin or levofloxacin), cycloserine, clofazimine, and pyrazinamide.To minimize potential toxicity, each regimen includes no more than two major QT-prolonging drugs (bedaquiline, clofazimine, and moxifloxacin). Treatment duration of the experimental regimens is 9 months. A 2-month extension of treatment is allowed with the presence of cavities at month 9 or in case of a positive culture at month 2. Baseline molecular drug susceptibility test (DST) of pyrazinamide will be performed using whole gene sequencing (WGS) technique. The result of molecular DST of pyrazinamide will be interpreted by technical staff at central laboratory of Huashan Hospital, Fudan University. Once a participant is proved resistant to pyrazinamide by WGS results at baseline, pyrazinamide will be discontinued with no need for extra drug replacement. The control regimen for RR-TB patients susceptible to fluoroquinolones is the current SOC oral regimen recommended by the national guidelines. Pre-XDR TB patients are identified with the Xpert MTB/XDR assay. The experimental arm is a 9-month regimen consisting of bedaquiline, cycloserine, clofazimine, linezolid, and pyrazinamide. Treatment extension to 11 months is allowed with the presence of cavities at month 9 or in case of a positive culture at month 2. Pyrazinamide will be discontinued from the study regimen if baseline molecular DST results reveal pyrazinamide resistance. The comparator is a conventional longer regimen (20 months) consistent with the national guidelines.

Conditions

• Multidrug Resistant Tuberculosis
• Rifampicin Resistant Tuberculosis
• Pre-XDR-TB

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Bdq(Lzd)+Lfx(Mfx)+Cfz(Cs)+Pto+E+H+Z	A-SOC: 4Bdq(Lzd)+Lfx(Mfx)+Cfz(Cs)+Pto+E+H+Z/5Lfx(Mfx)+Cfz(Cs)+E+Z During the intensive phase: Bedaquiline(Linezolid);Levofloxacin(Moxifloxacin) All treatment is taken orally
COMBINATION_PRODUCT	A1	9Bdq(6m)+Fq+Lzd+Cs+Cfz
COMBINATION_PRODUCT	A2a	9Bdq(6m)+Fq+Lzd(600mg)+Cs+Z
COMBINATION_PRODUCT	A2b	9Bdq(6m)+Fq+Lzd(2m)+Cs+Z
COMBINATION_PRODUCT	A2c	9Bdq(6m)+Fq+Lzd(600mg-300mg)+Cs+Z
COMBINATION_PRODUCT	A3	9Bdq(6m)+Fq+Lzd+Cfz+Z
COMBINATION_PRODUCT	A4	9Bdq(6m)+Fq+Cfz+Cs+Z
COMBINATION_PRODUCT	A5	9Fq+Lzd+Cfz+Cs+Z
COMBINATION_PRODUCT	B-SOC	6Bdq+Lzd+Cs+Cfz/14Lzd+Cfz+Cs
COMBINATION_PRODUCT	B1	9Bdq(6m)+Lzd+Cs+Cfz+Z

Timeline

• Start date: 2022-05-23
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2021-10-18
• Last updated: 2025-04-06

Locations

5 sites across 1 country: China