MDR-TBPhase 3FAST-MDRNCT07486024
Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France (FAST-MDR)
A Phase 3 study testing Bedaquiline Oral Tablet in people with MDR-TB and Tuberculosis Multi Drug Resistant Active, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MDR-TB, Tuberculosis Multi Drug Resistant Active, Antibiotic Resistance
- What is being tested?
- Bedaquiline Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 5 sitesFrance
- Study dates
- 11 Sep 2026to Feb 2032
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
CHU Amiens
Amiens
Claire ANDREJAK, MD, PhD, 03 22 08 79 98, andrejak.claire@chu-amiens.fr
- Recruiting
CHU Bichat - Claude-Bernard
Paris, 75018
Yousra KHERABI, MD, PhD, 01 40 25 78 20, yousra.kherabi@aphp.fr
- Not yet recruiting
Pitié-Salpêtrière Hospital - infectious and tropical diseases
Paris
Valérie POURCHER, 01 42 16 02 62, valerie.martinez@aphp.fr
- Recruiting
CHU Rennes
Rennes
François BENEZIT, MD-PhD, 02 99 28 95 64, Francois.BENEZIT@chu-rennes.fr
- Recruiting
CHU Toulouse - Hôpital Purpan
Toulouse, 31059
Guillaume MARTIN BLONDEL, MD, PhD, PU, 05 61 77 96 99, martin-blondel.g@chu-toulouse.fr
About this study
Official title: Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France - FAST-MDR
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.
Read the detailed description
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).
- Conditions
- MDR-TB, Tuberculosis Multi Drug Resistant Active, Antibiotic Resistance, Mycobacterium Tuberculosis
- Being tested
- Bedaquiline Oral Tablet
- Keywords
- MDR-TB, BPaLM, Tuberculosis Multi Drug Resistant
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bedaquiline Oral TabletDrug
Bedaquiline will be given as 400 mg once daily for 2 weeks and then 200 mg thrice weekly for the remaining 22 weeks
Bedaquiline Oral TabletDrug
Bedaquiline will be given as 200 mg once daily for 8 weeks and then 100 mg daily for the remaining 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Bedaquiline - 400 mg | Experimental | Posology : 400 mg once daily for 2 weeks and then 200 mg thrice weekly for the remaining 22 weeks. Receives: Drug: Bedaquiline Oral Tablet |
| Bedaquiline - 200 mg | Experimental | Posology : 200 mg once daily for 8 weeks and then 100 mg daily for the remaining 16 weeks. Receives: Drug: Bedaquiline Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness of BPaLM compared to conventional MDR-TB regimens
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)
Measured: Day 0 to Month 18
Secondary outcomes (22)
Early markers of BPaLM effectiveness (proportion of participants)
Proportion of participants with a negative sputum culture at two months after study treatment start
Measured: Day 0 to Day 60
Early markers of BPaLM effectiveness (time to sputum culture conversion)
Time to sputum culture conversion (defined as time between treatment start and the first of two consecutive negative sputum cultures, from specimens taken at least 7 days apart, as per WHO definitions)
Measured: Day 0 to month 18
BPaLM non-inferior effectiveness
For BPaLM arm, treatment success at 6 months, without addition of any TB drug or >4 consecutive weeks treatment interruption; For historical cohort: treatment success [all according to 2021 WHO definitions]
Measured: Start to month 6
BPaLM non-inferior effectiveness
For BPaLM arm, sustained treatment success at 12 months, without addition of any TB drug or >4 consecutive weeks treatment interruption; For historical cohort: treatment success [all according to 2021 WHO definitions]
Measured: Start to month 12
Rate of post-treatment relapse
For BPaLM arm, proportion of participants with TB relapse at 12 months after study treatment start.
For historical cohort: proportion of patients with TB relapse according to latest available post-treatment follow-up data
Measured: Start to month 12
Rate of post-treatment relapse
For BPaLM arm, proportion of participants with TB relapse at 18 months after study treatment start.
For historical cohort: proportion of patients with TB relapse according to latest available post-treatment follow-up data
Measured: Start to month 18
Factors associated with effectiveness of BPaLM at 18 month (interventional group only)
Factors associated with effectiveness of BPaLM at 18 months after study treatment start defined as patient characteristics, extension of TB disease, previous TB treatment, resistance profile and lineage of the TB strain, treatment adherence, and adverse events.
Measured: Start to month 18
Safety of BPaLM regimen
Proportion of participants with any serious adverse event [US FDA definition] or any Grade 3 or higher adverse event [CTCAE Severity Scale v 5.0]
Measured: Start to month 18
Pharmacology effectiveness (pharmacokinetic analyses)
Defined as population pharmacokinetic analyses for each drug
Measured: Start to month 6
Pharmacology effectiveness (evolution of MICs according to strain lineage)
Defined as multivariate models adjusting for MICs, strain lineage and patient factors to identify TDM measures associated, for each drug, with effectiveness, safety, and drug resistance acquisition
Measured: Start to month 6
Pharmacology effectiveness (evolution of MICs according to patient characteristics)
Defined as multivariate models adjusting for patient characteristics and extension of TB disease
Measured: Start to month 6
Rate of acquisition of drug resistance at 12 months (experimental group only)
Defined as the proportion of participants who acquired drug resistance to any of the study regimen drugs.
Measured: Start to month 12
Rate of acquisition of drug resistance at 18 months (each groups)
Defined as the proportion of participants who acquired drug resistance to any of the study regimen drugs.
Measured: Start to month 18
Microbiology eligibility - diagnostic delay (interventional group only)
Defined as time between screening and microbiological eligibilty assessment
Measured: Start to Month 1
Microbiology eligibility - diagnostic accuracy (interventional group only)
Defined as diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of different genotypic tests
Measured: Start to Month 1
Treatment adherence (interventional group only)
Proportion of doses taken out of total expected doses
Measured: Start to month 6
Health-related quality of life at treatment start (interventional group only)
Measured by Saint George's Respiratory questionnaire at treatment start
Measured: Start to month 1
Health-related quality of life at 6 months (interventional group only)
Measured by Saint George's Respiratory questionnaire at 6 months
Measured: Start to month 6
Health-related quality of life at 12 months (interventional group only)
Measured by Saint George's Respiratory questionnaire at 12 months
Measured: Start to month 12
Satisfaction of study participants
Measured by Likert scales at 12 months after study treatment start.
Measured: Start to month 12
Satisfaction of health care workers
Measured by Likert scales at 12 months after study treatment start.
Measured: Start to month 12
Health economy
Incremental cost per additional treatment success, calculated as: difference in costs (between groups)/ difference in treatment success (between groups).
Measured: Start to month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2026
- Study start11 Sep 2026
- Primary completionAug 2030 (estimated)
- Study completionFeb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MDR-TBStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study participants will be treated with a six-month treatment based on the combination of bedaquiline, linezolid, moxifloxacin and pretomanid (BPaLM), with the possible addition of clofazimine. All these drugs are routinely used for MDR-TB treatment, recommended by the WHO and other international guidelines, and approved by US FDA and EU EMA. The drugs will be given as follows: * Bedaquiline: 400 mg once daily for 2 weeks, then 200 mg thrice weekly; or 200 mg once daily for 8 weeks, then 100 mg once daily (dosing determined by randomization) * Clofazimine: 200 mg once daily for two weeks, then 100 mg once daily * Linezolid: 600 mg once daily * Moxifloxacin: 400 mg once daily * Pretomanid: 200 mg once daily
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Viatris Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07486024
- Sponsor's protocol ID
- APHP230852
- Acronym
- FAST-MDR
- Status last verified
- Mar 2026
- First submitted
- 18 Nov 2025
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.