The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 8 of 17 for:    mycobacterium abscessus
Previous Study | Return to List | Next Study

Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04310930
Recruitment Status : Recruiting
First Posted : March 17, 2020
Last Update Posted : August 8, 2023
Sponsor:
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
Hôpital Cochin
South Australian Health and Medical Research Institute
University of Melbourne
James Cook University, Queensland, Australia
Murdoch Childrens Research Institute
Information provided by (Responsible Party):
Claire Wainright, The University of Queensland

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Pulmonary Disease Due to Mycobacteria (Diagnosis) Drug: Amikacin Drug: Tigecycline Drug: Imipenem Drug: Cefoxitin Drug: Azithromycin Drug: Clarithromycin Drug: Clofazimine Drug: Ethambutol Drug: Linezolid Drug: co-trimoxazole Drug: Doxycycline Drug: Moxifloxacin Drug: Bedaquiline Drug: Rifabutin Phase 2 Phase 3

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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Masking Description:

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.
Primary Purpose: Treatment
Official Title: Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT)
Actual Study Start Date : March 2, 2020
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : August 31, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Intensive Therapy A
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
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

Drug: Tigecycline
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

Drug: Imipenem
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).

Drug: Cefoxitin
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.

Drug: Azithromycin

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.


Drug: Clarithromycin
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

Drug: Clofazimine
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.

Drug: Ethambutol
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.
Experimental: Intensive Therapy B
Following Randomisation 1, Participants will receive inhaled amikacin (IA), IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin AND clofazimine.
 Drug: Tigecycline
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

Drug: Imipenem
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).

Drug: Cefoxitin
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.

Drug: Azithromycin

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.


Drug: Clarithromycin
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

Drug: Clofazimine
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.

Drug: Ethambutol
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.

Drug: Amikacin
adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily
Experimental: Intensive Therapy C
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
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

Drug: Tigecycline
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

Drug: Imipenem
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).

Drug: Cefoxitin
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.

Drug: Azithromycin

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.


Drug: Clarithromycin
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

Drug: Ethambutol
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.
Active Comparator: Consolidation A
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

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.


Drug: Clarithromycin
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

Drug: Clofazimine
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.

Drug: Ethambutol
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.

Drug: Linezolid

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.


Drug: co-trimoxazole
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.

Drug: Doxycycline
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.

Drug: Moxifloxacin
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

Drug: Bedaquiline
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).

Drug: Rifabutin
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
Experimental: Consolidation B
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

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.


Drug: Clarithromycin
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

Drug: Clofazimine
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.

Drug: Ethambutol
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.

Drug: Amikacin
adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily

Drug: Linezolid

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.


Drug: co-trimoxazole
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.

Drug: Doxycycline
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.

Drug: Moxifloxacin
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

Drug: Bedaquiline
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).

Drug: Rifabutin
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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Appendix A1 - MABS clearance from respiratory samples with tolerance at final outcome [ Time Frame: 56 weeks for participants who received short intensive therapy and 62 weeks for participants who received prolonged intensive therapy. ]

    The probability of MABS clearance with good tolerance at final outcome. MABS clearance defined as: Negative MABS cultures from 4 consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy or a MABS negative BAL collected four weeks after completion of consolidation.

    Tolerance will be defined using 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 defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" as any adverse events coded as CTCAE grades 3, 4, or 5.


  2. Nested Study A1.1 Short Intensive Therapy - MABS Clearance [ Time Frame: Samples collected at 4 weeks and culture results determined at 6 weeks ]
    The number of patients in each group with microbiological clearance of MABS with good tolerance (in accordance with CTCAE). MABs clearance based on results from 3 sputum specimens or one BAL. Tolerance will be defined using 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 defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" as any adverse events coded as CTCAE grades 3, 4, or 5.

  3. Nested study A1.1.1 Efficacy of inhaled Amikacin during intensive therapy in comparison to intravenous Amikacin in the treatment of MABS-PD [ Time Frame: samples collected at 4 weeks and culture results determined at 6 weeks ]
    The number of patients in each group with microbiological clearance of MABS with good tolerability at completion of short intensive therapy with the use of inhaled amikacin (Arm B) and with the use of IV amikacin (Arm A) given during intensive phase. Clearance will be based on results from 3 consecutive sputum or 1 BAL sample.Tolerance will be defined using 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 defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" as any adverse events coded as CTCAE grades 3, 4, or 5.

  4. Nested Study A1.1.2 Efficacy of additional clofazimine during short intensive therapy in comparison to no additional clofazimine for treatment of MABS-PD [ Time Frame: samples collected at 4 weeks and culture results determined at 6 weeks ]
    The number of patients in each group with microbiological clearance of MABS with good tolerability at completion of short intensive therapy with the use of additional clofazimine (Arm A) and without the use of additional clofazimine (Arm C) given during intensive phase. Clearance will be based on results from 3 consecutive sputum or 1 BAL sample.Tolerance will be defined using 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 defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" as any adverse events coded as CTCAE grades 3, 4, or 5.

  5. Nested Study A1.2 - Comparison of microbiological clearance of MABS with good tolerability at 12 weeks in patients with MABS positive cultures at 6 weeks and allocated to prolonged intensive therapy and those allocated to consolidation therapy. [ Time Frame: samples collected at 10 weeks and culture results determined at 12 weeks ]
    The number of patients in each group with clearance of MABS at 12 weeks with good tolerance. Clearance will be based on the results of 3 consecutive sputum samples or 1 BAL sample.Tolerance will be defined using 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 defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" as any adverse events coded as CTCAE grades 3, 4, or 5.

  6. Nested Study 1.3 Consolidation Therapy - Comparison of MABS clearance between those allocated to consolidation therapy with oral treatment and those allocated to consolidation with oral therapy and additional inhaled amikacin [ Time Frame: 52 weeks or 58 weeks depending on clearance of MABS at 4 weeks, with those allocated to short IT completing at 52 weeks and those allocated to prolonged IT completing at 58 weeks. ]
    The number of patients with microbiological clearance of MABS with good tolerability between those allocated to consolidation therapy with oral treatment and those allocated to consolidation therapy with oral therapy and additional inhaled amikacin. MABS clearance based on 3 consecutive sputum samples or 1 BAL sample.Tolerance will be defined using 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 defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" as any adverse events coded as CTCAE grades 3, 4, or 5.


Secondary Outcome Measures :
  1. The probability of microbiological clearance of MABS at time point final, irrespective of toxicity for participants according to treatment path. [ Time Frame: 6 weeks, 12 weeks, at end of consolidation (52 and 58 weeks) and at final outcomes at 56 weeks and 62 weeks ]
    Probability of microbiological clearance irrespective of adverse event reporting.

  2. The safety of the treatment combinations in patients with MABS [ Time Frame: 6 weeks and 12 weeks and at end of consolidation (52 and 58 weeks) and after trial has been completed ]
    The number of participants with treatment-related adverse events as assessed by CTCAE version 5 at completion of short IT, at completion of prolonged IT, at completion of CT and at final outcomes.

  3. The relative change in FEV1 z-score between treatment groups for time point final compared with time point start in patients who do and who do not clear MABS at time point final. [ Time Frame: Day 0, 6 weeks, 12 weeks, at end of consolidation (52 and 58 weeks) and at final outcomes at 56 weeks and 62 weeks ]
    Relative change in FEV1 z score compared between treatment groups

  4. Change in % Bronchiectasis scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS [ Time Frame: Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path ]
    Change in % Bronchiectasis using PRAGMA CT between screening Day 0 and at 12 weeks and at final outcome

  5. Change in % Air Trapping scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS [ Time Frame: Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path ]
    Change in % Trapped Air using PRAGMA CT between screening Day 0 and at 12 weeks and at final outcome

  6. Change in % Disease scored using PRAGMA in chest CTs between Day 0 (screening) and at 12 weeks and at final outcome and between those who clear and those who do not clear MABS [ Time Frame: Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path ]
    Change in % Disease using PRAGMA CT between screening Day 0 and at 12 weeks and at final outcome

  7. The predictive value of structural abnormalities at Day 0 (screening) CTs for sputum conversion and for progression of structural changes in relation to therapy. [ Time Frame: Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path ]
    Association between structural abnormalities (%Bronchiectasis, %Air trapping and %Disease) at screening Day 0 and clearance of MABs at 12 weeks and at final outcome and with change in %Bronchiectasis, %Air trapping and %Disease between screening day 0 and at 12 weeks and at final outcome

  8. The change in CFQ-R respiratory domain for those with CF between treatment groups for short intensive, prolonged intensive and consolidation phases as well as between Day 0 and final outcome and between participants with and without MABS clearance. [ Time Frame: Day 0 and 6 weeks and 12 weeks, and at completion consolidation (at 52 and 58 weeks for those who completed short or prolonged IT) and at final outcome (at 56 and 62 weeks for those who completed short or prolonged IT) ]
    The change in CFQ-R respiratory domain for patients with CF between baseline and at 6 weeks, 12 weeks and 56 weeks for those that had short intensive therapy and 62 weeks for those who received prolonged intensive therapy

  9. The change in HRQOL in adults, between treatment groups for short intensive, prolonged intensive and consolidation phases as well as between Day 0 and final outcome and between participants with and without MABS clearance. [ Time Frame: Day 0 and 6 weeks and 12 weeks, and at completion consolidation (at 52 and 58 weeks for those who completed short or prolonged IT) and at final outcome (at 56 and 62 weeks for those who completed short or prolonged IT) ]
    Change in HRQOL measured using the SF36

  10. The change in HRQoL in Children between treatment groups for short intensive, prolonged intensive and consolidation phases as well as between Day 0 and final outcome and between participants with and without MABS clearance. [ Time Frame: Day 0 and 6 weeks and 12 weeks, and at completion consolidation (at 52 and 58 weeks for those who completed short or prolonged IT) and at final outcome (at 56 and 62 weeks for those who completed short or prolonged IT) ]
    Change in HRQOL measured using the Peds-QL™

  11. The cost effectiveness of the proposed treatment combinations across both intensive and consolidation phases of the trial. [ Time Frame: from date of randomization for the duration of treatment up to 56 weeks for those allocated to short IT and up to 62 weeks for those allocated to prolonged IT ]
    Total cost between treatments calculated as the sum product of health resource utilisation and resource unit price during treatment period.

  12. The change in six minute walk distance for adult participants from the date of randomization to up to 62 weeks according to treatment path and in participants who do and do not clear MABS at time point final. [ Time Frame: from date of randomization for the duration of treatment up to 56 weeks for those allocated to short IT and up to 62 weeks for those allocated to prolonged IT ]
    Change in 6 minute walk distance using the six minute walk test in adult participants


Other Outcome Measures:
  1. Examine the MABS clearance status at twelve (12 months) after time point final [ Time Frame: 12 months post trial completion ]
    To examine whether MABS has been cleared after 12 months completion of the trial using the 12 month follow up site Principal Investigator Questionnaire.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Intervention Cohort Inclusion Criteria:

  • Subjects with respiratory cultures positive for M. abscessus (MABS) (sub species abscessus, sub species bolletii, or subspecies massiliense) are required to meet all 3 American Thoracic Society criteria (clinical, radiological and microbiological) for MABS pulmonary disease (PD).
  • Subjects with mixed NTM infections (slow growers + MABS) (adding ethambutol will be permitted if required by the treating physician).
  • Willingness and ability to comply with trial regimens and the study visit requirements.

Intervention cohort Exclusion Criteria:

  • Receiving active treatment for MABS within the previous 12 months, except azithromycin for participants with cystic fibrosis and bronchiectasis.
  • Healthy volunteers may not participate.
  • Pregnancy or planning to continue breastfeeding
  • Known hypersensitivity to any of the therapies for which no alternate options(s) have been provided.

Observation Cohort Inclusion Criteria:

  • At least one positive respiratory MABS culture
  • Willingness and ability to comply with the study visit requirements.

Observation cohort Exclusion Criteria for:

  • Receiving active treatment for MABS within the previous 12 months, except azithromycin for participants with cystic fibrosis and bronchiectasis.
  • Healthy volunteers may not participate.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04310930


Contacts
Layout table for location contacts
Contact: Claire Wainwright, MD +61730697322 claire.wainwright@health.qld.gov.au
Contact: Kara Brady, MPharm +61730697618 FORMaTtrial@health.qld.gov.au

Locations
Show Show 38 study locations
Sponsors and Collaborators
The University of Queensland
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
Hôpital Cochin
South Australian Health and Medical Research Institute
University of Melbourne
James Cook University, Queensland, Australia
Murdoch Childrens Research Institute
  Study Documents (Full-Text)

Documents provided by Claire Wainright, The University of Queensland:
Study Protocol  [PDF] March 29, 2023

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Claire Wainright, Professor, The University of Queensland
ClinicalTrials.gov Identifier: NCT04310930    
Other Study ID Numbers: U1111-1209-0672
First Posted: March 17, 2020    Key Record Dates
Last Update Posted: August 8, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All de-identified raw data measured during the trial will be made available.
Supporting Materials: Study Protocol
Informed Consent Form (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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Claire Wainright, The University of Queensland:
Mycobacterium abscessus
Pulmonary disease
Microbiological
Regimen
 Radiological
Quality of life
Health economics
Biomarkers
Additional relevant MeSH terms:
Layout table for MeSH terms
Mycobacterium Infections
Lung Diseases
Respiratory Tract Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Moxifloxacin
Azithromycin
Clarithromycin
Doxycycline
Linezolid
Imipenem
Amikacin
 Ethambutol
Rifabutin
Tigecycline
Bedaquiline
Clofazimine
Trimethoprim, Sulfamethoxazole Drug Combination
Cefoxitin
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Synthesis Inhibitors