FORMaT: Finding the Optimal Regimen for Mycobacterium abscessus Treatment. A randomised, multi-arm, adaptive platform trial

Abstract

Objectives Mycobacterium abscessus (MABSC) are a group of rapidgrowing, multi-drug resistant non-tuberculous mycobacteria, which can cause pulmonary infection in those with underlying lung conditions, such as Cystic Fibrosis (CF). There is no current evidence to guide treatment for Mycobacterium abscessus pulmonary disease (MABSC-PD). The primary objective of this study is to determine the optimal treatment for patients with MABSC-PD. Methods FORMaT is an international, randomised, multi-arm, adaptive platform trial in adults and children, with or without CF. The trial consists of two participant groups; an intervention program that are randomised to treatment for MABSC-PD (for participants who fulfil American Thoracic Society (ATS) criteria for the diagnosis of MABSC-PD) and an observation cohort (participants who have at least one positive MABSC culture). The intervention program is an iterative, multi-stage platform trial with innovative and adaptive properties to evaluate different combinations of MABSC treatments. Patients enrolled into the observational cohort can transition into the intervention program, if they fulfil ATS criteria for MABSC-PD. The recruitment target is 300 and 150 participants for the intervention program and observation cohort respectively. Trial progress Recruitment is open in 12 sites including sites in Australia, Denmark and Singapore. The following countries are in set up: United Kingdom, France, Taiwan and Israel. As of January 2024, 30 participants have been recruited to the intervention arm and 19 participants to the observation cohort. Recruitment is ongoing. The first interim analysis is plannedforwhen60participants havecompletedthe interventionprogram. Conclusion Innovative trial designs and international collaboration are needed to provide the evidence to inform treatment decisions for rare conditions, such as MABS-PD. This trial aims to provide a platform for improving health outcomes for MABSC-PD patients.