Finding the optimal regimen for Mycobacteroides abscessus treatment (FOR Ma T) in people with Mycobacteroides abscessus pulmonary disease: a multicentre, randomised, multi-arm, adaptive platform trial
- PMID: 40976660
- PMCID: PMC12458872
- DOI: 10.1136/bmjopen-2024-096188
Finding the optimal regimen for Mycobacteroides abscessus treatment (FOR Ma T) in people with Mycobacteroides abscessus pulmonary disease: a multicentre, randomised, multi-arm, adaptive platform trial
Abstract
Introduction: Mycobacteroides abscessus (MABS) is within the non-tuberculous mycobacteria family. It inhabits soil and water, exhibits multi-antibiotic resistance and causes opportunistic lung infections, which may progress to symptomatic MABS-pulmonary disease (MABS-PD) associated with substantial morbidity, increased healthcare utilisation, impaired quality of life and increased mortality. Treatment regimens for MABS-PD are highly variable, not evidence-based and involve complex, expensive drug combinations administered for prolonged periods (>12 months) with frequent adverse effects and treatment failure. There is an urgent need for safe, efficacious and cost-effective MABS-PD therapy. Here, we describe the Master Protocol for the Finding the Optimal Regimen for Mycobacteroides abscessus Treatment (FORMaT) trial. FORMaT aims to determine the most effective and best tolerated treatment for MABS-PD as defined by MABS clearance from respiratory samples with good treatment tolerance.
Methods and analysis: FORMaT is an international multicentre, adaptive platform trial evaluating treatment combinations for MABS-PD. Participants are randomised multiple times during the trial, with assessment of the primary outcome of clearance of MABS infection with good treatment tolerance. Initially, therapies recommended in international consensus guidelines are being tested. Data obtained will eliminate therapies lacking efficacy or causing unacceptable toxicity. Novel treatments can then be added and tested against previously determined optimal approaches, leading in an iterative fashion to improved microbiological clearance and health outcomes. In parallel, an Observational cohort and several integrated and discovery studies are embedded in FORMaT to identify biomarkers of MABS-PD and MABS clearance, clinical and radiographic treatment response, drug pharmacokinetics and Mycobacteroides genomics and resistome.
Ethics and dissemination: The FORMaT Master Protocol and related documents are approved by regulatory authorities in each participating jurisdiction and/or site. Results will be published in peer-reviewed journals and presented at scientific meetings. De-identified, aggregated data will be shared on an approved online platform.
Trial registration numbers: NCT04310930, ANZCTR12618001831279, 2020-000050-10, ISRCTN67303903.
Keywords: clinical trial; cystic fibrosis; health economics; lung diseases; pulmonary disease; quality of life.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
Conflict of interest statement
Competing interests: TB received payments from Merck Sharp & Dohme to support a study of ceftolozane-tazobactam for bronchiectasis. TB is a member of the writing group for Therapeutic Guidelines and receives honoraria and travel expenses for four meetings per year. HLB received institutional grant funding from the University of Queensland via the Cystic Fibrosis Foundation (CFF) for the FORMaT study, in her role as UK Principal Investigator. HLB has also received institutional grants from LifeArc, CFF, the Cystic Fibrosis Trust, NIHR and Vertex. HLB holds patents issued outside the current work (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof. US-2016131648-A1; https://pubchem.ncbi.nlm.nih.gov/patent/US-2016131648-A1). HLB is Medical Director and co-founder of MiDx. SB received institutional payments from CFF (BELL19A0), the National Health and Medical Research Council (NHMRC), Australia (APP1102494) and the MRFF. SB also received institutional payments from Vertex Pharmaceuticals for speaking and chairing educational meetings between 2020 and 2022. SB received personal payments for travel costs from CFF (USA) in March 2023. SB holds unpaid roles on the iDSMB for the CLEAR Bronchiectasis study (Belfast, UK) and served as Chair of the iDSMB for the Ataxia-telangiectasia: treating mitochondrial dysfunction with a novel form of Anaplerosis trial (Brisbane, Australia), concluding in November 2023. SB is an unpaid board director at Gallipoli Medical Research and Health Translation Queensland. AB received payments to the Prince Charles Foundation from Merck Sharp & Dohme to support in vitro testing of imipenem-relebactam for M. abscessus infection. AB also received payments to the Sunshine Coast University Hospital Research Foundation from Merck Sharp & Dohme for a study of ceftolozane-tazobactam for bronchiectasis, and institutional payments to the Herston Infectious Diseases Institute from the CSIRO-Heidi grant for the Mycobacteria Acquisition from Potable Water (MAP) study. AB is a member of the Therapeutic Guidelines writing group and receives honoraria and travel expenses for three meetings per year. AB is an unpaid member of the iDSMB for the BEAT-CF study and is Chair of the Australasian Clinical Tuberculosis Network. DC received institutional payments from Vertex for lecturing and is Treasurer of the Netherlands Respiratory Society (unpaid position). JB received grants, consultancy fees and speaker fees from Roche, Abbott, Edwards Life Sciences, Sanofi, Moderna, VeinTech and Navi Medical Technologies, paid to his institution and unrelated to this study. JB also received support from NHMRC and MRFF grants, paid to his institution. KG received institutional payments from the MRFF (1152249), CFF (WAINWR19A0), several MRFF grants supporting studies on asthma, bronchiolitis and bronchiectasis, the EW 'AI' Thrasher grant award for bronchiectasis research and an Australian Research Council grant on airborne infection transmission. KG holds an honorary appointment on the iDSMB for an MRFF-supported adaptive platform trial on treating acute respiratory exacerbations in cystic fibrosis. KL received institutional payments from an NHMRC Investigator Grant (2017498), an NHMRC Career Development Fellowship (1127984) and an NHMRC Project Grant (1152249). TQ receives funding from the University of Queensland via a CFF grant for the FORMaT study in his role as Danish Principal Investigator. TQ has received payments for work on the Vertex Scientific Board and from Chiesi for speaker engagements. TQ holds an unpaid role as President of the Danish Society for Internal Medicine. JAR received project funding from the MRFF (1152249). GR received grant funding from the MRFF (2022/MRF2018745, 2020/MRF2001755) and NHMRC (2022GNT2020254). ARS has received research grants (paid to the University of Nottingham) from Vertex Pharmaceuticals and advisory board payments (also paid to the University of Nottingham) from Viatris Pharmaceuticals, all outside the current work. ARS holds patents issued outside the current work (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof. US-2016131648-A1; https://pubchem.ncbi.nlm.nih.gov/patent/US-2016131648-A1). ARS is a member of the DSMB for the North American Cystic Fibrosis Foundation Therapeutic Development Network. AT received salary for conceptualising the macrophage and mitochondria substudy, producing the standard operating procedures and conducting downstream work on the substudy. HAWMT received grants from IMI, NHMRC and CFF. Erasmus Medical Centre holds a royalty agreement for PRAGMA-CF. HAWMT has received consulting fees from Insmed and Novartis (paid to his institution) and from BI (paid directly). He received funding from Vertex for presenting at a Faculty Advance Course funded by Vertex, and travel support from Erasmus Medical Centre, Chiesi and Thirona to attend meetings and conferences. HAWMT is Chair of the ECFS Standardisation Committee. He was employed by Erasmus Medical Centre until 1 October 2023 and now holds an Emeritus Professor appointment. He became CMO of Thirona, Nijmegen, the Netherlands on 1 April 2022. RT received travel support from Beyond Air to present trial findings at the CHEST meeting in Nashville in 2022, and institutional payments from AN2 Therapeutics. RT held an unpaid role as ATS Assembly Chair and Board Member (2020–2022), is currently serving as Chair of the ATS Nominating Committee (2023–2024) and is an unpaid member of the ATS Membership Committee (2023–2024). CW is the Chief Investigator on the MRFF (1152249) grant and received institutional payments from the CFF (WAINWR19A0), the Children’s Hospital Foundation and the University of Queensland Cystic Fibrosis Programme Grant (50301). CW is an Associate Editor for Respirology and Thorax, and has received research funding and advisory board/consultancy payments from Vertex Pharmaceuticals, paid to the University of Queensland. All other authors have no conflicts of interest to declare.
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References
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