A multi-centre, randomised, multi-arm, adaptive platform trial in people with or without cystic fibrosis Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT)
Mycobacterium abscessus pulmonary disease
There are two phases of treatment for Mycobacterium abscessus (MABS): intensive therapy (IT) followed by consolidation therapy (CT). The initial interventional programme is randomised and open label. There are three stages of randomisation: 1. Randomisation to Short Intensive therapy (SI): At the start of the intensive phase, participants are randomised between one of three different intensive Arms A, B or C. Arm A. Intravenous (IV) amikacin, IV tigecycline, IV cefoxitin OR imipenem PLUS oral azithromycin OR oral clarithromycin AND oral clofazimine. Arm B. Inhaled amikacin (IA), IV tigecycline, IV cefoxitin OR imipenem PLUS oral azithromycin OR oral clarithromycin AND oral clofazimine. Arm C. IV amikacin, IV tigecycline, IV cefoxitin OR imipenem PLUS oral azithromycin OR oral clarithromycin. 2. Randomisation to Prolonged Intensive or Immediate Consolidation (PI/IC): The second randomisation will ONLY be for participants who are still MABS positive at the end of short intensive therapy (based on respiratory sampling collected at 4 weeks) and are able to continue with intensive therapy. Randomisation will occur at the end of short intensive therapy and will allocate participants to either: Continue intensive therapy which will be followed by consolidation (participants remain on the same intensive therapy drug regimen if randomised to prolonged intensive therapy), OR immediately commence consolidation therapy. 3. Randomisation to Consolidation: This randomisation will allocate participants to the consolidation therapy arms a or b for 46 weeks. Arm a. Oral clofazimine PLUS oral azithromycin OR oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin. Arm b. Inhaled amikacin (IA) AND oral clofazimine AND oral azithromycin OR oral clarithromycin in combination with one to three of the following oral antibiotic
Current inclusion criteria as of 25/06/2025: Eligibility criteria for the FORMaT trial can be applied at two levels: 1. Eligibility into the Intervention Program, or; 2. Eligibility into the Observational Cohort. Potential participants can only be enrolled in either the Intervention Program or the Observational Cohort at any one time. Provided the eligibility criteria are met, potential participants may either: 1. Enrol directly into the Intervention Program, or; 2. Enrol into the Observational Cohort and transition into the Intervention Program once they satisfy the inclusion criteria for this program which can occur at any time during the trial. Eligibility into the FORMaT trial will be assessed at screening. Observational Cohort participants who go on to meet the Intervention Program eligibility criteria can transition from the Observational Cohort to the Intervention Program. INTERVENTION PROGRAM ELIGIBILITY Potential participants are eligible for the Intervention Program if the criteria below are met. Eligible participants with mixed NTM infections (slow growers + MABS) or with recurrence of MABS infection following completion of previous treatment will be eligible if they meet the inclusion and exclusion criteria listed below. For eligible participants with mixed NTM infections additional therapy combinations are available as detailed in the relevant appendices. INTERVENTION PROGRAM INCLUSION CRITERIA 1. Positive MABS-PD diagnosis meeting all three American Thoracic Society clinical, radiological and microbiological diagnostic criteria for MABS-PD. Defined as: a. Clinical: Pulmonary symptoms and exclusion of other diagnoses. b. Radiological: Nodular or cavitary opacities on chest radiograph or a chest high-resolution computed tomography (HRCT) scan showing multifocal bronchiectasis with multiple small nodules. c. Microbiological: MABS positive culture results from at least two separate expectorated sputum samples. or Positive culture results from at least
Current exclusion criteria as of 25/06/2025: INTERVENTION PROGRAM EXCLUSION CRITERIA 1. Participants receiving current treatment for MABS (this includes drugs prescribed for the treatment of other mycobacteria and/or other indications that may have activity against MABS, as specified in the FORMaT Prohibited Drug List SOP), except for participants taking azithromycin as part of routine treatment for CF or chronic infection-related pulmonary disease, or as specified in the relevant appendix. 2. Participants who have a QTc interval of >500 milliseconds (QT interval corrected based on Fridericia method). 3. Participants who are pregnant or planning to continue breast feeding. 4. Known hypersensitivity or contraindication to any of the therapies for which no alternative option(s) have been provided. OBSERVATIONAL COHORT EXCLUSION CRITERIA Potential participants will be ineligible to participate in the Observational Cohort if any of the following criterion are met: Receiving active treatment for MABS within the previous 12 months (this includes drugs prescribed for the treatment of other mycobacteria and/or other indications that may have activity against MABS, as specified in the FORMaT Prohibited Drug List SOP, except for participants taking azithromycin as part of routine treatment for CF or chronic infection-related pulmonary disease). _____ Previous exclusion criteria: Intervention Program: 1. Participants receiving current treatment for MABS within the previous 12 months (this includes drugs prescribed for treatment of other mycobacteria and/or other indications that may have activity against MABS, as specified in FORMaT SOP 14, except for participants taking azithromycin as part of routine treatment for CF or chronic infection-related pulmonary disease) 2. Positive pregnancy test at any time during the FORMaT trial for females of childbearing potential 3. Breast-feeding 4. An unwillingness to comply with the acceptable methods of contraception, as described