Pulmonary Disease Due to Mycobacteria (Diagnosis)Phase 2/3FORMaTNCT04310930
Finding the Optimal Regimen for Mycobacterium Abscessus Treatment
A Phase 2/3 study testing Amikacin, Tigecycline and Imipenem in people with Pulmonary Disease Due to Mycobacteria (Diagnosis), run by The University of Queensland at 50 sites in 7 countries.
Trial summary
Mycobacterium abscessus (MABS) is a group of rapid-growing, multi-drug resistant non-tuberculous mycobacteria (NTM) causing infections in humans. MABS pulmonary disease (MABS-PD) can result in significant morbidity, increased healthcare utilisation, accelerated lung function decline, impaired quality of life, more… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pulmonary Disease Due to Mycobacteria (Diagnosis)
- What is being tested?
- Amikacin, Tigecycline and Imipenem
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 50 sitesin 7 countries
- Study dates
- 2 Mar 2020to 30 Jun 2030
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Eligibility criteria for the FORMaT trial can be applied at two levels:
- Eligibility into the Intervention Program, or;
- 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:
- Enrol directly into the Intervention Program, or;
- 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 (APPENDIX A) Potential participants are eligible for the Intervention Program (Appendix A) 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
- Positive MABS-PD diagnosis meeting all three American Thoracic Society clinical, radiological and microbiological diagnostic criteria for MABS-PD. Defined as:
- Clinical: Pulmonary symptoms and exclusion of other diagnoses.
- Radiological: Nodular or cavitary opacities on chest radiograph or a chest high-resolution computed tomography (HRCT) scan showing multifocal bronchiectasis with multiple small nodules.
- Microbiological: MABS positive culture results from at least two separate expectorated sputum samples. or Positive culture results from at least one bronchial wash or lavage. or Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or acid-fast bacilli (AFB)) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washes that are culture positive for NTM. Screening samples must be collected within the timeframes stated in the relevant appendix.
- Male or female participants of any age.
- Participant has not received treatment for MABS-PD in the 12 months preceding assessment of eligibility or as specified in the relevant appendix (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 Standard Operating Procedure (SOP)).
- Informed consent signed by participant or parent/legal guardian if participant is under 18 years of age.
- Ability to comply with study visits, therapies and study procedures as judged by the site investigator.
INTERVENTION PROGRAM EXCLUSION CRITERIA
- 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.
- Participants who have a QTc interval of >500 milliseconds (QT interval corrected based on Fridericia method).
- Participants who are pregnant or planning to continue breast feeding.
- Known hypersensitivity or contraindication to any of the therapies for which no alternative option(s) have been provided.
OBSERVATIONAL COHORT INCLUSION CRITERIA
To be eligible to participate in the Observational Cohort the following criteria must be met:
- Male and female participants of any age with at least one positive respiratory culture for MABS.
- Informed consent signed by participant or parent/legal guardian if participant is under 18 years of age.
- Ability to comply with study visits and study procedures as judged by the site investigator.
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).
ADDITIONAL ELIGIBILITY CRITERIA Mixed NTM infections Participants who have cultured slow growing NTM of the same species two or more times in the 24 months prior to screening, with one of those cultures within the 6 months prior to screening, will be considered to have mixed NTM infection at the time of screening. The participants must meet all other inclusion criteria and no exclusion criteria to be eligible for participation. Ethambutol may be used in addition to trial therapies to cover mixed NTM infections considered to require treatment by their clinician.
Appendix specific sub-studies and integrated studies Appendix specific sub-studies and integrated studies may have additional eligibility criteria which are described in each of the relevant appendices.
Trial locations and contacts
50 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
50 sites in 7 countries
Australia22 sites, 22 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide
- Recruiting
Sunshine Coast University Hospital
Birtinya
- Not yet recruiting
Royal Prince Alfred Hospital
Camperdown
- Recruiting
The Prince Charles Hospital
Chermside
- Recruiting
Gold Coast University Hospital
Gold Coast
- Recruiting
Greenslopes Private Hospital,
Greenslopes
- Recruiting
Austin Hospital
Heidelberg, Victoria
- Recruiting
St George Hospital
Kogarah, New South Wales
- Recruiting
Sir Charles Gairdiner Hospital
Nedlands
- Not yet recruiting
John Hunter Hospital
New Lambton
- Not yet recruiting
John Hunter Children's Hospital
New Lambton Heights
- Recruiting
Royal Melbourne Hospital
Parkville, Victoria
- Recruiting
Royal Perth Hospital
Perth, Western Australia, 6000
- Recruiting
Perth Children's Hospital
Perth
- Recruiting
The Alfred
Prahran
- Not yet recruiting
Sydney Children's Hospital
Randwick
- Recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Tiffany Jong, +61730697620, FORMaTtrial@health.qld.gov.au
- Recruiting
Mater Adult Hospital
South Brisbane
- Not yet recruiting
Macquarie University Hospital
Sydney
- Not yet recruiting
The Children's Hospital at Westmead
Westmead
- Not yet recruiting
Westmead Hospital
Westmead
- Recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland
United Kingdom17 sites, 17 recruiting
- Not yet recruiting
Belfast City Hospital
Belfast
- Not yet recruiting
Birmingham Children's Hospital
Birmingham
- Not yet recruiting
Birmingham Heartlands Hospital
Birmingham
- Not yet recruiting
Bristol Royal Hospital for Children
Bristol
- Not yet recruiting
Noah's Ark Childrens Hospital for Wales
Cardiff
- Not yet recruiting
Royal Hospital for Children and Young People, Edinburgh
Edinburgh
- Not yet recruiting
Western General Hospital
Edinburgh
- Not yet recruiting
Queen Elizabeth University Hospital, Glasgow
Glasgow
- Not yet recruiting
Alder Hey Children NHS Foundation Trust
Liverpool
- Not yet recruiting
Royal Brompton Hosptial
London
- Not yet recruiting
Royal Manchester Children's Hospital
Manchester
- Not yet recruiting
Nottingham Children's Hosptial
Nottingham
- Not yet recruiting
Queens Medical Centre
Nottingham
- Not yet recruiting
Welcome Wolfson Adult CF Centre (City Hospital Campus)
Nottingham
- Not yet recruiting
University Hospital Llandough
Penarth
- Not yet recruiting
Southampton General Hospital
Southampton
- Not yet recruiting
Wythenshawe Hospital
Wythenshawe
Israel6 sites, 6 recruiting
- Not yet recruiting
Soroka Medical Centre
Beer-Sheeva
- Not yet recruiting
Carmel Medical Centre
Haifa
- Not yet recruiting
Rambam Health Care Campus
Haifa
- Not yet recruiting
Hadassah Ein Kerem Hospital
Jerusalem
- Not yet recruiting
Schneider
Petah Tikva
- Not yet recruiting
Sheba Medical Centre
Ramat Gan Tel Aviv
Taiwan2 sites, 2 recruiting
- Not yet recruiting
Kaohsiung Medical University Hospital
Kaohsiung City
- Not yet recruiting
National Taiwan University Hospital
Taipei
Netherlands1 site, 1 recruiting
- Not yet recruiting
Erasmus MC Sophia Children's Hospital
Rotterdam
Singapore1 site, 1 recruiting
- Not yet recruiting
Tan Tock Seng Hospital Pte Ltd
Singapore, 308433
About this study
Official title: Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT)
Mycobacterium abscessus (MABS) is a group of rapid-growing, multi-drug resistant non-tuberculous mycobacteria (NTM) causing infections in humans. MABS pulmonary disease (MABS-PD) can result in significant morbidity, increased healthcare utilisation, accelerated lung function decline, impaired quality of life, more challenging lung transplantation, and increased mortality. While the overall numbers affected is small, the prevalence of infections is increasing worldwide. The Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT) trial aims to produce high quality evidence for the best treatment regimens to maximise health outcomes and minimise toxicity and treatment burden, as well as developing biomarkers (serology, gene expression signatures, and radiology) to guide decisions for starting treatment and measuring disease severity in patients with MABS PD.
Read the detailed description
Mycobacterium abscessus (MABS) are a group of non-tuberculous mycobacteria (NTM) found in water and soil habitats that exhibit high levels of intrinsic multi-drug resistance. They are recognised opportunistic human pathogens capable of causing chronic pulmonary disease (MABS-PD), predominantly in individuals with underlying inflammatory lung diseases.
Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT) is an iterative, standing, platform trial with innovative and adaptive properties that evaluate and develop the optimal combinations of therapies for children and adults with MABS-PD to clear MABS infection with acceptable tolerance. We will use these opportunities afforded by the clinical trial platform to establish discovery studies to: (i) understand the effects of disease and treatment on health-related quality of life, (ii) determine cost effectiveness of interventions, (iii) optimise pharmacokinetic drug dosing, (iv) understand susceptibility to MABs-PD, (v) develop biomarkers of clinical disease, (vi) investigate genomics of MABs strains causing MABs-PD and development of antimicrobial resistance.
FORMaT provides a pragmatic design to address challenges to develop an evidence base for the first time for MABS-PD. Initially, the trial has been designed to test therapies that are currently the basis for treatment guidelines for MABS-PD. The trial has the capacity to add new treatments and to eliminate therapies because of futility as they either lack efficacy or cause unacceptable toxicity. Novel therapeutic approaches are then tested against the previously determined optimal approaches, thus leading in an iterative fashion to improve microbiological clearance, and health outcomes associated with MABS-PD. The trial is designed as a series of trials within the main trial to enable investigation of the different phases of treatment; intensive (intravenous treatment phase) and consolidation (oral and or inhaled treatment phase) based on clinical guidelines. The primary outcome for each trial is microbiological clearance with clinical tolerance (Grade 1 or 2) based on Common Terminology Criteria for Adverse Events (version 5). This enables subjects to continue in the trial even if tolerance is poor or they change treatments in a specific phase of the trial as those events contribute to the primary outcome determination.
- Being tested
- Amikacin, Tigecycline, Imipenem, Cefoxitin, Azithromycin
- Keywords
- Mycobacterium abscessus, Pulmonary disease, Microbiological, Regimen, Radiological, Quality of life, Health economics, Biomarkers
- Medical subject headings
- Disease, Mycobacterium Infections, Nontuberculous, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmikacinDrug
Adults: Intravenous amikacin 5mg/kg once daily or 7.5mg/kg twice daily or 20-25 mg/kg thrice weekly. Children:Intravenous amikacin 15-30 mg/kg once daily, maximum dose 1500mg
TigecyclineDrug
Adults: Intravenous Tigecycline 25 mg increasing by 5 mg every two doses until either maximum dose reached (50mg) or until patient is unable to tolerate twice daily. Children (≥8 years of age) intravenous tigecycline: Day 1- 0.6mg/kg twice daily to a maximum of 25mg. Day 2- 0.6mg/kg (maximum 25mg) in the morning, 1.2 mg/kg (maximum 50mg) at night. Day 3- 1.2mg/kg (maximum 50 mg) twice daily
ImipenemDrug
Adults: Intravenous Imipenem (≥50kg) 500mg twice daily (<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated).
CefoxitinDrug
Adults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily.
AzithromycinDrug
Adults: Oral azithromycin 500mg (≥40kg) once daily, (<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (<40kg) 250mg thrice weekly.
Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg.
ClarithromycinDrug
Adult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: <8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily
ClofazimineDrug
Adult: Oral clofazimine 100mg once daily. Children: Oral clofazimine: 3-5mg/kg once daily. Maximum dose of 50mg once daily if <40kg or 100mg if ≥40kg once daily.
EthambutolDrug
Adults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily.
AmikacinDrug
adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily
LinezolidDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily.
Children: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Age 1 week - 9 years 10mg/kg twice daily maximum dose of 300mg. Age 10-12 years 10mg/kg twice daily maximum dose of 600mg. >12 years 600mg once daily.
co-trimoxazoleDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral Co-trimoxazole (TMP-SMX) 160/800mg twice daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral co-trimoxazole 5mg TMP/kg maximum dose of 160mg TMP/ 800mg SMX twice daily.
DoxycyclineDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline 100mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline (ages ≥ 8 years) 2mg/kg once daily maximum dose 100mg.
MoxifloxacinDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 400mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg
BedaquilineDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months).
RifabutinDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin 5mg/kg once daily
| Study group | Role | What they receive |
|---|---|---|
| Intensive Therapy A | Active comparator | Following Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin AND clofazimine. Receives: Drug: Amikacin; Drug: Tigecycline; Drug: Imipenem; Drug: Cefoxitin; Drug: Azithromycin; Drug: Clarithromycin; Drug: Clofazimine; Drug: Ethambutol |
| Intensive Therapy B | Experimental | Following Randomisation 1, Participants will receive inhaled amikacin (IA), IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin AND clofazimine. Receives: Drug: Tigecycline; Drug: Imipenem; Drug: Cefoxitin; Drug: Azithromycin; Drug: Clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: Amikacin |
| Intensive Therapy C | Experimental | Following Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin. Receives: Drug: Amikacin; Drug: Tigecycline; Drug: Imipenem; Drug: Cefoxitin; Drug: Azithromycin; Drug: Clarithromycin; Drug: Ethambutol |
| Consolidation A | Active comparator | Oral clofazimine + oral azithromycin/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. Receives: Drug: Azithromycin; Drug: Clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: Linezolid; Drug: co-trimoxazole; Drug: Doxycycline; Drug: Moxifloxacin; Drug: Bedaquiline; Drug: Rifabutin |
| Consolidation B | Experimental | Inhaled amikacin (IA), oral clofazimine + oral azithromycin/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. Receives: Drug: Azithromycin; Drug: Clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: Amikacin; Drug: Linezolid; Drug: co-trimoxazole; Drug: Doxycycline; Drug: Moxifloxacin; Drug: Bedaquiline; Drug: Rifabutin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome of the Intervention Program is microbiological clearance of MABS with good tolerance of the interventions.
The primary outcome of the Intervention Program is microbiological clearance of MABS with good tolerance of the interventions.
Definition of MABS clearance at final outcome:
Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation.
Definition of tolerance:
Tolerance is based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug will be assessed in the determination of tolerance. "Good" tolerance is defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" tolerance is defined as any adverse events attributed as possibly-, probably-, or definitely-related to study drug coded as CTCAE grades 3, 4, or 5.
Measured: Screening (Day 0) to End of treatment plus four weeks off-treatment (Final Outcome Visit (Week 56 for those allocated to Immediate Consolidation or Week 62 for those allocated to Prolonged Intensive).
Nested Study A1.1 Type of Short Intensive Therapy - MABS clearance from respiratory sample(s) with tolerance.
To compare the microbiological clearance of MABS from respiratory samples collected at 4 weeks with good tolerability assessed at the end of short intensive therapy between the use of Inhaled Amikacin (Arm B) and the use of Intravenous Amikacin (Arm A) given during intensive phase. Definition of MABS clearance is 3 MABS negative sputum samples or ONE MABS negative Bronchoalveolar Lavage (BAL) at end of Short Intensive Therapy. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
Measured: Screening (Day 0) to the End of Short Intensive Therapy (Week 6).
Nested Study A1.2 - Duration of intensive therapy for patients completing short intensive treatment with ongoing positive MABS cultures collected at 4 weeks and randomised to either a further 6 weeks intensive therapy or immediate consolidation.
To compare the microbiological clearance from samples collected at 10 weeks with good tolerability between those who are allocated to prolonged intensive therapy and those allocated to immediate consolidation following short intensive therapy.
MABS clearance, assessed at the end of prolonged intensive therapy (for those allocated to prolonged intensive) or at 12 weeks (for those allocated to immediate consolidation) will be defined as negative MABS cultures from all 3 sputum samples or from one BAL sample collected at 10 weeks. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
Measured: Screening (Day 0) to EITHER the End of Prolonged Intensive Therapy (for those allocated to Prolonged Intensive) OR Week 12 Visit (for those allocated to immediate consolidation therapy).
Nested Study 1.3 Consolidation Therapy - The use of oral therapy only or oral therapy and inhaled amikacin for consolidation therapy.
To compare the microbiological clearance with good tolerability of MABS between those allocated to consolidation therapy with oral treatment and those allocated to consolidation therapy with oral treatment and additional Inhaled Amikacin at Final Outcome.
Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
Measured: Start of Consolidation Therapy (Date of Randomisation to Consolidation Therapy) to End of Treatment plus 4 weeks off treatment (Final Outcome Visit - Week 56 for those randomised to Immediate Consolidation or Week 62 for those in Prolonged Intensive).
Secondary outcomes (15)
Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway.
Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway. Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation.
Measured: Screening (Day 0); at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Safety of treatment combinations based on adverse event reporting.
Safety of treatment combinations based on the reporting of adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drugs.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Safety of treatments based on changes in microbiological resistance.
Safety of treatments based on changes to microbiological resistance of the MABS bacteria during the study treatment period.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in FEV1 z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome.
Change in FEV1 z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Phenotype of the structural abnormalities of chest CTs and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome.
Phenotype of the structural abnormalities of chest CTs and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome.
Measured: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment.
Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment.
Measured: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the CFQ-R) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the CFQ-R) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. CFQ-R is the Cystic Fibrosis Questionnaire Revised and will be completed by all CF participants.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the EQ-5D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the EQ-5D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. EQ-5D is the EuroQol 5 Dimensions and will be completed by all participants.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the SGRQ) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the SGRQ) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. SGRQ is the St George's Respiratory Questionnaire and will be completed by all non-CF participants who are 18 years and older.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the SF-36) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the SF-36) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. The SF-36 is the Short-Form 36 questionnaire and will be completed by all participants 16 years and older.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the PedsQL) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the PedsQL) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. The PedsQL is the Pediatric Quality of Life Inventory questionnaire and will be completed by participants 2 years old to 16 years old.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the CHU-9D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the CHU-9D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. CHU-9D is the Child Health Utility 9D and will be completed by all children aged 7 to 17 years of age.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Cost effectiveness of the treatment combinations (measured using the Costs Questionnaire and Linked Administrative Healthcare Utilisation Data (for applicable jurisdictions)) across intensive and consolidation phases of the trial.
Cost effectiveness of the treatment combinations across intensive and consolidation phases of the trial. Cost effectiveness of the treatments will be assessed using the unvalidated "Costs Questionnaire" and where applicable and available, the linked administrative healthcare utilisation data e.g. in Australian participants.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Causes for early withdrawal from MABS-PD treatment due to reasons other than poor tolerance as defined in the primary objectives.
Causes for early withdrawal from MABS-PD treatment due to reasons other than poor tolerance as defined in the primary objectives.
Measured: At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2020
- Study start2 Mar 2020
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease Due to Mycobacteria (Diagnosis)Studies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- There are 2 different phases of treatment; intensive therapy (IT) followed by consolidation therapy (CT). Intervention cohort participants will be randomised to 1 of 3 treatment arms for 6 weeks of IT. After the first 6 weeks of IT participants who are culture positive for MABS are randomised to either prolonged IT (additional 6 weeks of IT) then CT, or to commence CT. If, at week 6 participants are MABS culture-negative they will commence CT. Participants commencing CT are randomised to one of two treatment arms for 50 weeks. There are 12 possible paths through the trial. This standing platform trial design enables assessment of short IT, prolonged IT, and CT components individually as well as the overall combination of IT and CT. After 100 patients have completed short IT an interim analysis will be conducted, and Bayesian adaptive randomisation (BAR) will be implemented. New interventions may be added or stopped in the future due to lack of benefit at interim analyses.
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Queensland
- Sponsor type
- University, hospital or other
- Collaborators
- Australian Government Department of Health and Ageing, Children's Hospital Foundation, Cystic Fibrosis Foundation, Newcastle University, Griffith University, Erasmus Medical Center, Monash University, University of Copenhagen, South Australian Health and Medical Research Institute, University of Melbourne, Murdoch Childrens Research Institute, QIMR Berghofer Medical Research Institute
- Responsible party
- Principal investigator, Claire Wainright, The University of Queensland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04310930
- Sponsor's protocol ID
- U1111-1209-0672
- Acronym
- FORMaT
- Status last verified
- May 2026
- First submitted
- 28 Feb 2020
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All de-identified raw data measured during the trial will be made available.
Publications
Jong T, Baird T, Barr HL, Bell S, Bigirumurame T, Brady K, Burke A, Byrnes J, Caudri D, Clark JE, Coin LJM, Goh F, Grimwood K, Hicks D, Jayawardana K, Joshi S, Lee K, Qvist T, Reid D, Rice M, Roberts JA, Rogers G, Shackleton C, Sly PD, Smyth AR, Stevens L, Stockwell R, Tarique A, Taylor S, Thomson R, Tiddens HAWM, Wang XF, Wason J, Wainwright C. Finding the optimal regimen for Mycobacteroides abscessus treatment (FORMaT) in people with Mycobacteroides abscessus pulmonary disease: a multicentre, randomised, multi-arm, adaptive platform trial. BMJ Open. 2025 Sep 21;15(9):e096188. doi: 10.1136/bmjopen-2024-096188.
PubMed 40976660
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT)
- ClinicalTrials.gov ID
- NCT04310930
- Acronym / sponsor ID
- FORMaT / U1111-1209-0672
- Keywords
- Mycobacterium abscessus, Pulmonary disease, Microbiological, Regimen, Radiological, Quality of life, Health economics, Biomarkers
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- The University of QueenslandUniversity, hospital or other
- Collaborators
- Australian Government Department of Health and Ageing, Children's Hospital Foundation, Cystic Fibrosis Foundation, Newcastle University, Griffith University, Erasmus Medical Center, Monash University, University of Copenhagen, South Australian Health and Medical Research Institute, University of Melbourne, Murdoch Childrens Research Institute, QIMR Berghofer Medical Research Institute
- Study start
- 2 Mar 2020 (actual)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 17 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mycobacterium abscessus (MABS) is a group of rapid-growing, multi-drug resistant non-tuberculous mycobacteria (NTM) causing infections in humans. MABS pulmonary disease (MABS-PD) can result in significant morbidity, increased healthcare utilisation, accelerated lung function decline, impaired quality of life, more challenging lung transplantation, and increased mortality. While the overall numbers affected is small, the prevalence of infections is increasing worldwide. The Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT) trial aims to produce high quality evidence for the best treatment regimens to maximise health outcomes and minimise toxicity and treatment burden, as well as developing biomarkers (serology, gene expression signatures, and radiology) to guide decisions for starting treatment and measuring disease severity in patients with MABS PD.
Detailed description
Mycobacterium abscessus (MABS) are a group of non-tuberculous mycobacteria (NTM) found in water and soil habitats that exhibit high levels of intrinsic multi-drug resistance. They are recognised opportunistic human pathogens capable of causing chronic pulmonary disease (MABS-PD), predominantly in individuals with underlying inflammatory lung diseases.
Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT) is an iterative, standing, platform trial with innovative and adaptive properties that evaluate and develop the optimal combinations of therapies for children and adults with MABS-PD to clear MABS infection with acceptable tolerance. We will use these opportunities afforded by the clinical trial platform to establish discovery studies to: (i) understand the effects of disease and treatment on health-related quality of life, (ii) determine cost effectiveness of interventions, (iii) optimise pharmacokinetic drug dosing, (iv) understand susceptibility to MABs-PD, (v) develop biomarkers of clinical disease, (vi) investigate genomics of MABs strains causing MABs-PD and development of antimicrobial resistance.
FORMaT provides a pragmatic design to address challenges to develop an evidence base for the first time for MABS-PD. Initially, the trial has been designed to test therapies that are currently the basis for treatment guidelines for MABS-PD. The trial has the capacity to add new treatments and to eliminate therapies because of futility as they either lack efficacy or cause unacceptable toxicity. Novel therapeutic approaches are then tested against the previously determined optimal approaches, thus leading in an iterative fashion to improve microbiological clearance, and health outcomes associated with MABS-PD. The trial is designed as a series of trials within the main trial to enable investigation of the different phases of treatment; intensive (intravenous treatment phase) and consolidation (oral and or inhaled treatment phase) based on clinical guidelines. The primary outcome for each trial is microbiological clearance with clinical tolerance (Grade 1 or 2) based on Common Terminology Criteria for Adverse Events (version 5). This enables subjects to continue in the trial even if tolerance is poor or they change treatments in a specific phase of the trial as those events contribute to the primary outcome determination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- There are 2 different phases of treatment; intensive therapy (IT) followed by consolidation therapy (CT). Intervention cohort participants will be randomised to 1 of 3 treatment arms for 6 weeks of IT. After the first 6 weeks of IT participants who are culture positive for MABS are randomised to either prolonged IT (additional 6 weeks of IT) then CT, or to commence CT. If, at week 6 participants are MABS culture-negative they will commence CT. Participants commencing CT are randomised to one of two treatment arms for 50 weeks. There are 12 possible paths through the trial. This standing platform trial design enables assessment of short IT, prolonged IT, and CT components individually as well as the overall combination of IT and CT. After 100 patients have completed short IT an interim analysis will be conducted, and Bayesian adaptive randomisation (BAR) will be implemented. New interventions may be added or stopped in the future due to lack of benefit at interim analyses.
| Arm | Type | Receives |
|---|---|---|
| Intensive Therapy A | Active comparator | Drug: Amikacin, Drug: Tigecycline, Drug: Imipenem, Drug: Cefoxitin, Drug: Azithromycin, Drug: Clarithromycin, Drug: Clofazimine, Drug: EthambutolFollowing Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin AND clofazimine. |
| Intensive Therapy B | Experimental | Drug: Tigecycline, Drug: Imipenem, Drug: Cefoxitin, Drug: Azithromycin, Drug: Clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: AmikacinFollowing Randomisation 1, Participants will receive inhaled amikacin (IA), IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin AND clofazimine. |
| Intensive Therapy C | Experimental | Drug: Amikacin, Drug: Tigecycline, Drug: Imipenem, Drug: Cefoxitin, Drug: Azithromycin, Drug: Clarithromycin, Drug: EthambutolFollowing Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin. |
| Consolidation A | Active comparator | Drug: Azithromycin, Drug: Clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: Linezolid, Drug: co-trimoxazole, Drug: Doxycycline, Drug: Moxifloxacin, Drug: Bedaquiline, Drug: RifabutinOral clofazimine + oral azithromycin/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. |
| Consolidation B | Experimental | Drug: Azithromycin, Drug: Clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: Amikacin, Drug: Linezolid, Drug: co-trimoxazole, Drug: Doxycycline, Drug: Moxifloxacin, Drug: Bedaquiline, Drug: RifabutinInhaled amikacin (IA), oral clofazimine + oral azithromycin/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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmikacinAdults: Intravenous amikacin 5mg/kg once daily or 7.5mg/kg twice daily or 20-25 mg/kg thrice weekly. Children:Intravenous amikacin 15-30 mg/kg once daily, maximum dose 1500mg | Drug | Intensive Therapy A, Intensive Therapy C |
| TigecyclineAdults: Intravenous Tigecycline 25 mg increasing by 5 mg every two doses until either maximum dose reached (50mg) or until patient is unable to tolerate twice daily. Children (≥8 years of age) intravenous tigecycline: Day 1- 0.6mg/kg twice daily to a maximum of 25mg. Day 2- 0.6mg/kg (maximum 25mg) in the morning, 1.2 mg/kg (maximum 50mg) at night. Day 3- 1.2mg/kg (maximum 50 mg) twice daily | Drug | Intensive Therapy A, Intensive Therapy B, Intensive Therapy C |
| ImipenemAdults: Intravenous Imipenem (≥50kg) 500mg twice daily (<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated). | Drug | Intensive Therapy A, Intensive Therapy B, Intensive Therapy C |
| CefoxitinAdults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily. | Drug | Intensive Therapy A, Intensive Therapy B, Intensive Therapy C |
| AzithromycinAdults: Oral azithromycin 500mg (≥40kg) once daily, (<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (<40kg) 250mg thrice weekly. Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg. | Drug | Consolidation A, Consolidation B, Intensive Therapy A, Intensive Therapy B, Intensive Therapy C |
| ClarithromycinAdult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: <8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily | Drug | Consolidation A, Consolidation B, Intensive Therapy A, Intensive Therapy B, Intensive Therapy C |
| ClofazimineAdult: Oral clofazimine 100mg once daily. Children: Oral clofazimine: 3-5mg/kg once daily. Maximum dose of 50mg once daily if <40kg or 100mg if ≥40kg once daily. | Drug | Consolidation A, Consolidation B, Intensive Therapy A, Intensive Therapy B |
| EthambutolAdults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily. | Drug | Consolidation A, Consolidation B, Intensive Therapy A, Intensive Therapy B, Intensive Therapy C |
| Amikacinadult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily | Drug | Consolidation B, Intensive Therapy B |
| LinezolidAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily. Children: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Age 1 week - 9 years 10mg/kg twice daily maximum dose of 300mg. Age 10-12 years 10mg/kg twice daily maximum dose of 600mg. >12 years 600mg once daily. | Drug | Consolidation A, Consolidation B |
| co-trimoxazoleAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral Co-trimoxazole (TMP-SMX) 160/800mg twice daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral co-trimoxazole 5mg TMP/kg maximum dose of 160mg TMP/ 800mg SMX twice daily. | Drug | Consolidation A, Consolidation B |
| DoxycyclineAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline 100mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline (ages ≥ 8 years) 2mg/kg once daily maximum dose 100mg. | Drug | Consolidation A, Consolidation B |
| MoxifloxacinAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 400mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg | Drug | Consolidation A, Consolidation B |
| BedaquilineAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months). | Drug | Consolidation A, Consolidation B |
| RifabutinAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin 5mg/kg once daily | Drug | Consolidation A, Consolidation B |
Primary outcome
The primary outcome of the Intervention Program is microbiological clearance of MABS with good tolerance of the interventions.
Time frame: Screening (Day 0) to End of treatment plus four weeks off-treatment (Final Outcome Visit (Week 56 for those allocated to Immediate Consolidation or Week 62 for those allocated to Prolonged Intensive).
The primary outcome of the Intervention Program is microbiological clearance of MABS with good tolerance of the interventions. Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation. Definition of tolerance: Tolerance is based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug will be assessed in the determination of tolerance. "Good" tolerance is defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" tolerance is defined as any adverse events attributed as possibly-, probably-, or definitely-related to study drug coded as CTCAE grades 3, 4, or 5.
Nested Study A1.1 Type of Short Intensive Therapy - MABS clearance from respiratory sample(s) with tolerance.
Time frame: Screening (Day 0) to the End of Short Intensive Therapy (Week 6).
To compare the microbiological clearance of MABS from respiratory samples collected at 4 weeks with good tolerability assessed at the end of short intensive therapy between the use of Inhaled Amikacin (Arm B) and the use of Intravenous Amikacin (Arm A) given during intensive phase. Definition of MABS clearance is 3 MABS negative sputum samples or ONE MABS negative Bronchoalveolar Lavage (BAL) at end of Short Intensive Therapy. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
Nested Study A1.2 - Duration of intensive therapy for patients completing short intensive treatment with ongoing positive MABS cultures collected at 4 weeks and randomised to either a further 6 weeks intensive therapy or immediate consolidation.
Time frame: Screening (Day 0) to EITHER the End of Prolonged Intensive Therapy (for those allocated to Prolonged Intensive) OR Week 12 Visit (for those allocated to immediate consolidation therapy).
To compare the microbiological clearance from samples collected at 10 weeks with good tolerability between those who are allocated to prolonged intensive therapy and those allocated to immediate consolidation following short intensive therapy. MABS clearance, assessed at the end of prolonged intensive therapy (for those allocated to prolonged intensive) or at 12 weeks (for those allocated to immediate consolidation) will be defined as negative MABS cultures from all 3 sputum samples or from one BAL sample collected at 10 weeks. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
Nested Study 1.3 Consolidation Therapy - The use of oral therapy only or oral therapy and inhaled amikacin for consolidation therapy.
Time frame: Start of Consolidation Therapy (Date of Randomisation to Consolidation Therapy) to End of Treatment plus 4 weeks off treatment (Final Outcome Visit - Week 56 for those randomised to Immediate Consolidation or Week 62 for those in Prolonged Intensive).
To compare the microbiological clearance with good tolerability of MABS between those allocated to consolidation therapy with oral treatment and those allocated to consolidation therapy with oral treatment and additional Inhaled Amikacin at Final Outcome. Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
15 secondary outcomes
Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway.
Time frame: Screening (Day 0); at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Safety of treatment combinations based on adverse event reporting.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Safety of treatments based on changes in microbiological resistance.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in FEV1 z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Phenotype of the structural abnormalities of chest CTs and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment.
Time frame: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the CFQ-R) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the EQ-5D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the SGRQ) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the SF-36) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the PedsQL) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the CHU-9D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Cost effectiveness of the treatment combinations (measured using the Costs Questionnaire and Linked Administrative Healthcare Utilisation Data (for applicable jurisdictions)) across intensive and consolidation phases of the trial.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Causes for early withdrawal from MABS-PD treatment due to reasons other than poor tolerance as defined in the primary objectives.
Time frame: At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Background: PubMed 40976660Jong T, Baird T, Barr HL, Bell S, Bigirumurame T, Brady K, Burke A, Byrnes J, Caudri D, Clark JE, Coin LJM, Goh F, Grimwood K, Hicks D, Jayawardana K, Joshi S, Lee K, Qvist T, Reid D, Rice M, Roberts JA, Rogers G, Shackleton C, Sly PD, Smyth AR, Stevens L, Stockwell R, Tarique A, Taylor S, Thomson R, Tiddens HAWM, Wang XF, Wason J, Wainwright C. Finding the optimal regimen for Mycobacteroides abscessus treatment (FORMaT) in people with Mycobacteroides abscessus pulmonary disease: a multicentre, randomised, multi-arm, adaptive platform trial. BMJ Open. 2025 Sep 21;15(9):e096188. doi: 10.1136/bmjopen-2024-096188.
- Individual participant dataSharing planned: Yes. All de-identified raw data measured during the trial will be made available.
Related trials for Pulmonary Disease Due to Mycobacteria (Diagnosis)
Enrolling by invitationObservational study
To Evaluate the Clinical Efficacy and Safety of Omadacycline in the Treatment of Mycobacterium Abscessus Infection.
Mycobacterium Abscessus Infection, NTM Lung Infection Due to MAC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
50 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Amikacin, Tigecycline and Imipenem in people with Pulmonary Disease Due to Mycobacteria (Diagnosis), run by The University of Queensland at 50 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in Australia, United Kingdom, Israel, Taiwan, Denmark and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Claire Wainwright, MD (+61730697322, claire.wainwright@health.qld.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome of the Intervention Program is microbiological clearance of MABS with good tolerance of the interventions. (time frame: Screening (Day 0) to End of treatment plus four weeks off-treatment (Final Outcome Visit (Week 56 for those allocated to Immediate Consolidation or Week 62 for those allocated to Prolonged Intensive).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04310930, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.