Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France (FAST-MDR)

Prior treatment

• Is unable to take oral drugs
• Is taking or needs to take contraindicated medications in association with investigational medicinal products

Other illness

• Has known allergies, hypersensitivity or intolerance or any other medical condition and contra indications to any drug of the regimen
• Has ≥500 msec QTcF interval on any ECG taken at screening or baseline visits, or has any cardiac risk factor for severe arrhythmia
• Is already on a MDR/RR-TB treatment regimen since 4 weeks or more, and has no need to change the treatment regimen (i.e. adverse events, treatment failure)
• Has any other condition (social or medical) which, in the opinion of the site investigator, would make the study participant unsafe

Lab values

• Has significant and uncorrectable lab abnormalities at baseline: haemoglobin ≤7.9 g/dL, platelet count \<75 000/mm3; absolute neutrophil count \<1 000/ mm3; potassium \<3.0 mEq/L; serum creatinine \>3 x upper level of normality (ULN); alanine aminotransferase (ALT) ≥3 x ULN

Other

• Unwilling to comply to study procedures, at the clinician appreciation
• Has proven or likely resistance to bedaquiline, clofazimine, linezolid, pretomanid or moxifloxacine, or has had exposure (for 30 days or more) in past five years to bedaquiline, clofazimine, delamanid, linezolid, or pretomanid
• Has severe extrapulmonary TB, including meningo-encephalitis, brain abscess, osteo-arthritis, osteomyelitis
• Is concurrently participating in another trial of any medicinal product
• Has peripheral neuropathy of grade 3 or 4 (CTCAE scale)
• Is known to be pregnant or is unwilling or unable to stop breastfeeding an infant
• Individuals permanently legally incompetent adults, under judicial or administrative protection and vulnerable persons

• Is 18 years old or more
• Is affected by bacteriologically- or molecularly-confirmed tuberculosis, due to strains of M. tuberculosis resistant to rifampicin (with or without resistance to isoniazid) according to a rapid molecular test
• Is willing and able to give informed consent to be enrolled in the research project (signed or witnessed consent if the patient is illiterate)
• Patients seen in consultation or hospitalized in one of the centers involved for rifampicin-resistant TB, with screening results available and compatible within 14 days following consent signature;
• Is willing to use effective\* contraception: women with childbearing potential\*\* must agree to use effective contraception, unless their partner has had a vasectomy, for the duration of study treatment and up to 6 months after the end of study treatment; men who have not had a vasectomy must agree to use effective contraception for the duration of study treatment and up to 3 months after the end of study treatment;
  • The following contraception methods are considered effective, according to local regulation (CTFG recommendations, March 2024):
  • Combined hormonal contraception (oestrogen + progestin)
  • Progestin-only hormonal contraception
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomised partner
  • A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Is affiliated to a social security system (as beneficiary) or has state medical aid (AME) or has an ongoing demand for AMEor has an ongoing demand for an emergency medical care (dispositif de soins d'urgence, as applicable for tuberculosis)