Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France - FAST-MDR
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 6
- 主要终点
- Effectiveness of BPaLM compared to conventional MDR-TB regimens
研究概览
简要总结
The FAST-MDR trial is an externally-controlled, multicentre trial with one prospective arm, evaluating the non-inferiority of the effectiveness of BPaLM in the interventional arm versus the effectiveness of the long, conventional regimen in a French historical cohort of MDR-TB patients (2006-2022). In light of recent WHO recommendations suggesting using BPaLM as a first choice for routine MDR-TB treatment and of the expected benefits of BPaLM over the standard treatment, there will be no internal comparator arm in the study.
详细描述
This study will be conducted in all adult patients diagnosed at the study sites with rifampicin-resistant tuberculosis.
The study will assess a treatment strategy, with the regimen being adapted to the result of rapid molecular testing and phenotypic DST for fluoroquinolone resistance. Study participants will perform a rapid molecular test for fluoroquinolone resistance at screening/baseline visit: if the result is susceptible, they will receive BPaLM; if the result is resistant, they will receive a regimen with clofazimine instead of moxifloxacin (BPaLC); if the result is inconclusive, they will receive BPaLM plus clofazimine (BPaLMC). In this latter case, the regimen will be adapted according to result of phenotypic DST for fluoroquinolones: in case of susceptibility, clofazimine will be dropped (BPaLM); in case of resistance, moxifloxacin will be dropped (BPaLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •Is unable to take oral drugs
- •Has known allergies, hypersensitivity or intolerance or any other medical condition and contra indications to any drug of the regimen
- •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
- •Is taking or needs to take contraindicated medications in association with investigational medicinal products
- •Has ≥500 msec QTcF interval on any ECG taken at screening or baseline visits, or has any cardiac risk factor for severe arrhythmia
- •Has severe extrapulmonary TB, including meningo-encephalitis, brain abscess, osteo-arthritis, osteomyelitis
- •Is concurrently participating in another trial of any medicinal product
- •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 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
- •Has peripheral neuropathy of grade 3 or 4 (CTCAE scale)
- •Has any other condition (social or medical) which, in the opinion of the site investigator, would make the study participant unsafe
- •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
研究组 & 干预措施
Bedaquiline - 400 mg
Posology : 400 mg once daily for 2 weeks and then 200 mg thrice weekly for the remaining 22 weeks.
干预措施: Bedaquiline Oral Tablet (Drug)
Bedaquiline - 200 mg
Posology : 200 mg once daily for 8 weeks and then 100 mg daily for the remaining 16 weeks.
干预措施: Bedaquiline Oral Tablet (Drug)
结局指标
主要结局
Effectiveness of BPaLM compared to conventional MDR-TB regimens
时间窗: Day 0 to Month 18
Proportion of study participants achieving sustained treatment success at 18 months after study treatment start, according to 2021 WHO definitions, in the absence of permanent addition of any TB drug to the regimen or \>4 consecutive weeks treatment interruption. For the historical cohort: proportion of patients achieving treatment success (2021 WHO definitions)
次要结局
- Satisfaction of study participants(Start to month 12)
- Early markers of BPaLM effectiveness (proportion of participants)(Day 0 to Day 60)
- Early markers of BPaLM effectiveness (time to sputum culture conversion)(Day 0 to month 18)
- BPaLM non-inferior effectiveness(Start to month 6)
- BPaLM non-inferior effectiveness(Start to month 12)
- Rate of post-treatment relapse(Start to month 12)
- Rate of post-treatment relapse(Start to month 18)
- Factors associated with effectiveness of BPaLM at 18 month (interventional group only)(Start to month 18)
- Safety of BPaLM regimen(Start to month 18)
- Pharmacology effectiveness (pharmacokinetic analyses)(Start to month 6)
- Pharmacology effectiveness (evolution of MICs according to strain lineage)(Start to month 6)
- Pharmacology effectiveness (evolution of MICs according to patient characteristics)(Start to month 6)
- Rate of acquisition of drug resistance at 12 months (experimental group only)(Start to month 12)
- Rate of acquisition of drug resistance at 18 months (each groups)(Start to month 18)
- Microbiology eligibility - diagnostic delay (interventional group only)(Start to Month 1)
- Microbiology eligibility - diagnostic accuracy (interventional group only)(Start to Month 1)
- Treatment adherence (interventional group only)(Start to month 6)
- Health-related quality of life at treatment start (interventional group only)(Start to month 1)
- Health-related quality of life at 6 months (interventional group only)(Start to month 6)
- Health-related quality of life at 12 months (interventional group only)(Start to month 12)
- Satisfaction of health care workers(Start to month 12)
- Health economy(Start to month 18)