Innovating(IN) Shorter(S), All- Oral, Precised(P), Individualized(I) Treatment Regimen(RE) for Rifampicin Resistant Tuberculosis(INSPIRE-TB)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Bdq(Lzd)+Lfx(Mfx)+Cfz(Cs)+Pto+E+H+Z, A1, A2a, A2b.
- Who it may be relevant to
- Registry conditions: Multidrug Resistant Tuberculosis, Rifampicin Resistant Tuberculosis, Pre-XDR-TB. Basic parameters: 16 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Interventions
- 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
Primary outcome measures
- a favorable outcome at the end of study [Time frame: at 21 months after randomization]
Secondary outcome measures (6)
- The median time to sputum culture conversion [Time frame: at 21 months after randomization]
- The proportion of participants with grade 3 or higher AEs, SAEs [Time frame: at 21 months after randomization]
- All-cause mortality and treatment relevant mortality [Time frame: at 21 months after randomization]
- The proportion of participants with treatment relevant SAEs [Time frame: at 21 months post-randomization]
- The proportion of participants with grade 3 or higher QTc prolongation [Time frame: at 21 months after randomization]
- The proportion of participants experiencing permanent drug discontinuation or replacement due to QTc prolongation [Time frame: at 21 months after randomization]
Eligibility criteria
Inclusion criteria
- Male or female patients aged 16-75 years with weight over 30kg, regardless of HIV status;
- Pulmonary TB with rifampicin resistance diagnosed with either WHO-approved rapid molecular diagnostic test or phenotype drug susceptibility test (within 60 days prior to randomisation) ;
- Signed informed consent form (ICF).
Exclusion criteria
- Known allergies, hypersensitivity, or contraindication to any of the study drugs as described in additional material;
- Participants combined with central nervous system TB, tuberculous osteomyelitis or arthritis, hematogenous disseminated pulmonary TB;
- Patients known to be pregnant or breastfeeding at the time of enrollment;
- Patients who have received second-line MDR-TB treatment for 14 days or more prior to enrollment;
- Patients in critical condition and expected survival is estimated by physician to be less than 12 weeks.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 5 centers
- Guiyang Public Health Treatment Center — Guiyang
- People's Hospital of Qiandongnan — Kaili
- The Third People's Hospital of Liupanshui — Liupanshui
- Affiliated Hospital of Zunyi Medical University — Zunyi
- Huashan Hospital of Fudan University — Shanghai
Identifiers
NCT: NCT05081401 · INSPIRE-TB