Finding the Optimal Regimen for Mycobacterium Abscessus Treatment

NCT04310930 | Recruiting Phase 2 DMC

• 1 other identifier: U1111-1209-0672
• Study Type: interventional
• Target: 300
• Locations: 7 countries
• Sites: 50

Brief 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 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.

Conditions

Pulmonary Disease Due to Mycobacteria (Diagnosis)

Keywords

Mycobacterium abscessus; Pulmonary disease; Microbiological; Regimen; Radiological; Quality of life; Health economics; Biomarkers

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

Other Outcomes (1)

• Participant's MABS clearance status 12 months after Final Outcome.

  12 months after End of Treatment plus 4 weeks off treatment (Final Outcome Visit).

Study Arms (5)

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.

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.

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.

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.

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.

Drug: Azithromycin; Drug: Clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: Amikacin; Drug: Linezolid; Drug: co-trimoxazole; Drug: Doxycycline; Drug: Moxifloxacin; Drug: Bedaquiline; Drug: Rifabutin

Interventions

Amikacin DRUG

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

Intensive Therapy A; Intensive Therapy C

Tigecycline DRUG

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

Intensive Therapy A; Intensive Therapy B; Intensive Therapy C

Imipenem DRUG

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).

Intensive Therapy A; Intensive Therapy B; Intensive Therapy C

Cefoxitin DRUG

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.

Intensive Therapy A; Intensive Therapy B; Intensive Therapy C

Azithromycin DRUG

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.

Consolidation A; Consolidation B; Intensive Therapy A; Intensive Therapy B; Intensive Therapy C

Clarithromycin DRUG

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

Consolidation A; Consolidation B; Intensive Therapy A; Intensive Therapy B; Intensive Therapy C

Clofazimine DRUG

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.

Consolidation A; Consolidation B; Intensive Therapy A; Intensive Therapy B

Ethambutol DRUG

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.

Consolidation A; Consolidation B; Intensive Therapy A; Intensive Therapy B; Intensive Therapy C

Linezolid DRUG

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.

Consolidation A; Consolidation B

co-trimoxazole DRUG

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.

Consolidation A; Consolidation B

Doxycycline DRUG

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.

Consolidation A; Consolidation B

Moxifloxacin DRUG

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

Consolidation A; Consolidation B

Bedaquiline DRUG

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).

Consolidation A; Consolidation B

Rifabutin DRUG

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

Consolidation A; Consolidation B

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Positive MABS-PD diagnosis meeting all three American Thoracic Society clinical, radiological and microbiological diagnostic criteria for MABS-PD. Defined as:
• 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.
• 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.
• 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.

Sponsors & Collaborators

• The University of Queensland: lead
• Australian Government Department of Health and Ageing: collaborator
• Children's Hospital Foundation: collaborator
• Cystic Fibrosis Foundation: collaborator
• Newcastle University: collaborator
• Griffith University: collaborator
• Erasmus Medical Center: collaborator
• Monash University: collaborator
• University of Copenhagen: collaborator
• South Australian Health and Medical Research Institute: collaborator
• University of Melbourne: collaborator
• Murdoch Childrens Research Institute: collaborator
• QIMR Berghofer Medical Research Institute: collaborator

Study Sites (50)

St George Hospital

Kogarah, New South Wales, Australia

RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

RECRUITING

Austin Hospital

Heidelberg, Victoria, Australia

RECRUITING

Royal Melbourne Hospital

Parkville, Victoria, Australia

RECRUITING

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, Australia

RECRUITING

Sunshine Coast University Hospital

Birtinya, Australia

RECRUITING

Royal Prince Alfred Hospital

Camperdown, Australia

NOT YET RECRUITING

The Prince Charles Hospital

Chermside, Australia

RECRUITING

Gold Coast University Hospital

Gold Coast, Australia

RECRUITING

Greenslopes Private Hospital,

Greenslopes, Australia

RECRUITING

Sir Charles Gairdiner Hospital

Nedlands, Australia

RECRUITING

John Hunter Hospital

New Lambton, Australia

NOT YET RECRUITING

John Hunter Children's Hospital

New Lambton Heights, Australia

NOT YET RECRUITING

Perth Children's Hospital

Perth, Australia

RECRUITING

The Alfred

Prahran, Australia

RECRUITING

Sydney Children's Hospital

Randwick, Australia

NOT YET RECRUITING

Mater Adult Hospital

South Brisbane, Australia

RECRUITING

Macquarie University Hospital

Sydney, Australia

NOT YET RECRUITING

The Children's Hospital at Westmead

Westmead, Australia

NOT YET RECRUITING

Westmead Hospital

Westmead, Australia

NOT YET RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Soroka Medical Centre

Beer-Sheeva, Israel

NOT YET RECRUITING

Carmel Medical Centre

Haifa, Israel

NOT YET RECRUITING

Rambam Health Care Campus

Haifa, Israel

NOT YET RECRUITING

Hadassah Ein Kerem Hospital

Jerusalem, Israel

NOT YET RECRUITING

Schneider

Petah Tikva, Israel

NOT YET RECRUITING

Sheba Medical Centre

Ramat Gan Tel Aviv, Israel

NOT YET RECRUITING

Erasmus MC Sophia Children's Hospital

Rotterdam, Netherlands

NOT YET RECRUITING

Tan Tock Seng Hospital Pte Ltd

Singapore, 308433, Singapore

NOT YET RECRUITING

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

NOT YET RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

NOT YET RECRUITING

Belfast City Hospital

Belfast, United Kingdom

NOT YET RECRUITING

Birmingham Children's Hospital

Birmingham, United Kingdom

NOT YET RECRUITING

Birmingham Heartlands Hospital

Birmingham, United Kingdom

NOT YET RECRUITING

Bristol Royal Hospital for Children

Bristol, United Kingdom

NOT YET RECRUITING

Noah's Ark Childrens Hospital for Wales

Cardiff, United Kingdom

NOT YET RECRUITING

Royal Hospital for Children and Young People, Edinburgh

Edinburgh, United Kingdom

NOT YET RECRUITING

Western General Hospital

Edinburgh, United Kingdom

NOT YET RECRUITING

Queen Elizabeth University Hospital, Glasgow

Glasgow, United Kingdom

NOT YET RECRUITING

Alder Hey Children NHS Foundation Trust

Liverpool, United Kingdom

NOT YET RECRUITING

Royal Brompton Hosptial

London, United Kingdom

NOT YET RECRUITING

Royal Manchester Children's Hospital

Manchester, United Kingdom

NOT YET RECRUITING

Nottingham Children's Hosptial

Nottingham, United Kingdom

NOT YET RECRUITING

Queens Medical Centre

Nottingham, United Kingdom

NOT YET RECRUITING

Welcome Wolfson Adult CF Centre (City Hospital Campus)

Nottingham, United Kingdom

NOT YET RECRUITING

University Hospital Llandough

Penarth, United Kingdom

NOT YET RECRUITING

Southampton General Hospital

Southampton, United Kingdom

NOT YET RECRUITING

Wythenshawe Hospital

Wythenshawe, United Kingdom

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 40976660 DERIVED

MeSH Terms

Conditions

Disease; Mycobacterium Infections, Nontuberculous; Lung Diseases

Interventions

Amikacin; Tigecycline; Imipenem; Cefoxitin; Azithromycin; Clarithromycin; Clofazimine; Ethambutol; Linezolid; Trimethoprim, Sulfamethoxazole Drug Combination; Doxycycline; Moxifloxacin; bedaquiline; Rifabutin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Kanamycin; Aminoglycosides; Glycosides; Carbohydrates; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephamycins; Cephalosporins; Thiazines; Sulfur Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Phenazines; Heterocyclic Compounds, 3-Ring; Ethylenediamines; Diamines; Polyamines; Amines; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Benzene Derivatives; Sulfones; Trimethoprim; Pyrimidines; Drug Combinations; Pharmaceutical Preparations; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds

Central Study Contacts

Claire Wainwright, MD

CONTACT

+61730697322; claire.wainwright@health.qld.gov.au

Kara Brady, MPharm

CONTACT

+61730697618; FORMaTtrial@health.qld.gov.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The FORMAT trial may include placebo controlled double blind randomised interventions in the future, but the initial intervention program is randomised but open label. There will be three stages of randomisation in the intervention program of this study, dictating the treatment the participant will receive. Randomisation at each level will be conducted using the method of minimisation. Each randomisation level will be planned to enable flexibility via pre-planned adaptations.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 17, 2020
• Study Start: March 2, 2020
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Immediately following publication with no end date.
• Access Criteria: Data will be made available to recognised academic institutes and clinical teams upon written request with a proposal for data usage to Chief Investigator, Professor Claire Wainwright

Locations

GB (17); IL (6); SG (1); AU (22); NL (1); DK (1); TW (2)