ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618001831279

Ethics application status

Approved

Date submitted

9/02/2018

Date registered

9/11/2018

Date last updated

16/11/2023

Date data sharing statement initially provided

9/11/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT)

Scientific title

Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT)

Secondary ID [1]

ClinicalTrials.gov Identifier NCT04310930

Universal Trial Number (UTN)

U1111-1209-0672

Trial acronym

FORMaT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Mycobacterium abscessus pulmonary disease

Mycobacterium abscessus

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Human Genetics and Inherited Disorders

Cystic fibrosis

Infection

Other infectious diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study is a standing platform trial to evaluate the efficacy of antibiotic therapy combinations in clearing Mycobacterium abscessus pulmonary disease (MABS-PD). The study will provide a pipeline for new therapies to be evaluated for treating MABS-PD in all age groups.

There are two different phases of treatment; intensive therapy followed by consolidation therapy. Intervention cohort participants will be randomised to 1 of 3 treatment arms for 6 weeks of intensive therapy. After the first 6 weeks of intensive therapy participants who are culture positive for MABS are randomised to either prolonged intensive therapy (additional 6 weeks of intensive therapy) then consolidation therapy, or to commence consolidation therapy. If, at week 6 participants are MABS culture-negative they will commence consolidation therapy. Participants commencing consolidation therapy are randomised to one of two treatment arms for 50 weeks. There are 12 possible paths through the trial and they are detailed below:
1. Intensive Arm A for 6 weeks, Consolidation arm b for 46 weeks,
2. Intensive Arm A for 12 weeks, Consolidation arm b for 46 weeks,
3. Intensive Arm A for 6 weeks, “Consolidation: arm a” for 46 weeks,
4. Intensive Arm A for 12 weeks, “Consolidation: arm a” for 46 weeks,
5. Intensive Arm B for 6 weeks, Consolidation arm b for 46 weeks,
6. Intensive Arm B for 12 weeks, Consolidation arm b for 46 weeks,
7. Intensive Arm B for 6 weeks, “Consolidation: arm a” for 46 weeks,
8. Intensive Arm B for 12 weeks, “Consolidation: arm a” for 46 weeks,
9. Intensive Arm C for 6 weeks, Consolidation arm b for 46 weeks,
10. Intensive Arm C for 12 weeks, Consolidation arm b for 46 weeks,
11. Intensive Arm C for 6 weeks, “Consolidation: arm a” for 46 weeks,
12. Intensive Arm C for 12 weeks, “Consolidation: arm a” for 46 weeks,
Where Intensive Arm A is IV amikacin, and; IV tigecycline, and; IV imipenem/cilastatin or IV cefoxitin, and; Oral azithromycin or oral clarithromycin, and; Oral clofazimine.
Intensive Arm B is Inhaled amikacin, and; IV tigecycline, and; IV imipenem/cilastatin or IV cefoxitin, and; Oral azithromycin or oral clarithromycin, and; Oral clofazimine.
Intensive Arm C is IV amikacin, and; IV tigecycline, and; IV imipenem/cilastatin or IV cefoxitin, and; Oral azithromycin or oral clarithromycin.
Consolidation arm a is Oral clofazimine, and; Oral azithromycin or oral clarithromycin, and; In combination with one to three of the following oral antibiotics: Oral linezolid, Oral trimethoprim / sulfamethoxazole, Oral bedaquiline, Oral rifabutin, Oral doxycycline, Oral moxifloxacin.
Consolidation arm b is Inhaled amikacin, and; Oral clofazimine, and; Oral azithromycin or oral clarithromycin, and; In combination with one to three of the following oral antibiotics: Oral linezolid, Oral trimethoprim / sulfamethoxazole, Oral bedaquiline, Oral rifabutin, Oral doxycycline, Oral moxifloxacin.
Dosing recommendations for each drug is outlined in the Drug dosing Regimen Tables contained in the relevant sections of the FORMaT Intervention Program Appendix A1 and Appendix A2 modules.

This standing platform trial design enables assessment of short intensive therapy, prolonged intensive therapy, and consolidation therapy components individually as well as the overall combination of intensive therapy and consolidation therapy. After 100 patients have completed short intensive therapy 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.

Those participants that have a positive respiratory specimen but do not meet all three ATS criteria or those who are MABS-PD positive but are not commencing drug therapy can be recruited into the observation cohort where they will undergo all the same monitoring and outcomes collection but will not receive treatment. If they meet ATS criteria at a later stage during the trial they may be randomised into the active treatment phases (intensive and consolidation) of the trial.

The FORMaT trial has several substudies that are conducted alongside the main trial. These substudies are registered on a separate trial registration.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The active comparator group are those intervention program participants who are treated according to current therapy guidelines (Intensive arm A). Active comparator treatment for the intensive phase is (based on current guidelines): IV amikacin + IV tigecycline + IV imipenem or IV cefoxitin (guided by local susceptibility testing and patient specific hypersensitivity) + oral azithromycin or oral clarithromycin AND clofazimine..
See attachment 1 for the drug dosing regimens for the intensive treatment phase for both paediatrics and adults

Control group

Active

Outcomes

Primary outcome [1]

MABS clearance from respiratory samples with tolerance at final outcome - 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.

Timepoint [1]

MABS clearance will be measured at week4 of intensive therapy for all intervention cohort participants. Participants with a MABS positive respiratory sample will be randomised 1:1 to either continue intensive therapy or, commence consolidation therapy. Participants randomised to an additional 6 weeks of intensive therapy will continue in the same treatment arm they were randomised to during the first six weeks of treatment. A respiratory sample will be collected at week 12 to determine MABS clearance following prolonged intensive therapy.. This intensive phase is followed by consolidation treatment during which time four respiratory samples will be collected at weeks 18, 28, 38 and 58 (final week of consolidation therapy).. The final time point and the primary endpoint in this treatment group will be measured one month after consolidation therapy, at week 62. Those intervention participants with a positive MABS sample at week 4 who are randomised to the immediate consolidation phase will have respiratory samples collected at week 18, 28, 38 and 52 (final week of consolidation therapy). The final time point and the primary endpoint in this treatment group will be measured one month after consolidation therapy at week 56. Participants with a negative MABS respiratory sample at week 4 will be randomised to the consolidation treatment phase for 46 weeks. Respiratory samples will be collected at week 18, 28, 38 and 52 (final week of consolidation therapy). The final time point and the primary endpoint in this treatment group will be measured one month after consolidation therapy at week 56 post-treatment commencement for participants who were randomised to immediate consolidation therapy, and at week 62 post-treatment commencement for participants randomised to prolonged intensive therapy.

Primary outcome [2]

A1.1 Short Intensive Therapy - MABS Clearance - 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.

Timepoint [2]

Primary outcome [3]

A1.1.1 Efficacy of inhaled Amikacin during intensive therapy in comparison to intravenous Amikacin in the treatment of MABS-PD - 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.

Timepoint [3]

MABS clearance is assessed from the culture results of respiratory samples collected at 4 we
eks post treatment commencement (results of respiratory sample culture available at 6 weeks). Tolerance is assessed at 6 weeks post treatment commencement. MABS clearance is assessed from the culture results of respiratory samples collected at 4 we
eks post treatment commencement (results of respiratory sample culture available at 6 weeks). Tolerance is assessed at 6 weeks post treatment commencement.

Secondary outcome [1]

A1.1.2 Efficacy of additional clofazimine during short intensive therapy in comparison to no additional clofazimine for treatment of MABS-PD - 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. This outcome is part of the FORMaT trial primary outcomes

Timepoint [1]

Secondary outcome [2]

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. - 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. . This outcome is part of the FORMaT trial primary outcomes.

Timepoint [2]

MABS clearance is assessed from the culture results of respiratory samples collected at 10 weeks post treatment commencement (results of respiratory sample culture available at 12 weeks). Tolerance is assessed at 12 weeks post treatment commencement.

Secondary outcome [3]

A1.3 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 - 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. This outcome is part of the FORMaT trial primary outcomes.

Timepoint [3]

MABS clearance and tolerance will be assessed at 52 weeks post-treatment initiation or 58 weeks post-treatment initiation depending on clearance of MABS at 4 weeks, with those allocated to short intensive therapy being assessed at 52 weeks post-treatment initiation and those allocated to prolonged intensive therapy being assessed at 58 weeks post-treatment initiation.

Secondary outcome [4]

The probability of microbiological clearance (based on 3 consecutive sputum samples or 1 BAL) of MABS irrespective of toxicity for participants according to treatment path at the end of short intensive therapy at 6 weeks, at 12 weeks, at completion of consolidation and at final outcome.

Timepoint [4]

6 weeks, 12 weeks, at end of consolidation (52 and 58 weeks) and at final outcomes at 56 weeks and 62 weeks.

Secondary outcome [5]

The safety of the treatment combinations in patients with MABS - The number of participants with treatment-related adverse events as assessed by CTCAE version 5 at completion of: short intensive treatment, prolonged intensive treatment, consolidation treatment and at final outcome.

Timepoint [5]

6 weeks and 12 weeks and at end of consolidation (at 52 or 58 weeks depending on if participant was randomised to immediate consolidation or prolonged intensive) and when the trial has been completed at either Week 56 or Week 62 (depending on whether participant was randomised to immediate consolidation or prolonged intensive therapy).

Secondary outcome [6]

The relative change in FEV1 (measured using spirometry) z-score between treatment groups for short intensive, prolonged intensive and consolidation phases of the trial as well as between Day 0 and final outcome and between participants with and without clearance of MABS.

Timepoint [6]

Day 0, 6 weeks, 12 weeks, at end of consolidation (52 and 58 weeks) and at final outcomes at 56 weeks and 62 weeks.

Secondary outcome [7]

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.

Timepoint [7]

Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path.

Secondary outcome [8]

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

Timepoint [8]

Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path

Secondary outcome [9]

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.

Timepoint [9]

Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path

Secondary outcome [10]

The structural changes on chest CT (%Bronchiectasis, %Air trapping and %Disease) at baseline will be used to ascertain if they are associated with sputum conversion ie clearance of MABS and with progression or change in structural changes (%Bronchiectasis, %Air trapping and %Disease).

Timepoint [10]

Day 0 and 12 weeks and at final outcome at either 56 weeks or 62 weeks according to treatment path

Secondary outcome [11]

The change in Cystic Fibrosis Questionnaire-Revised (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.

Timepoint [11]

Day 0 and 6 weeks and 12 weeks, and at completion consolidation (at 52 and 58 weeks for those who completed short or prolonged intensive therapy) and at final outcome (at 56 and 62 weeks for those who completed short or prolonged intensive therapy]

Secondary outcome [12]

The change in health related quality of life (HRQoL) in adults measured using the SF-36, 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.

Timepoint [12]

Secondary outcome [13]

Change in health related quality of life (HRQoL) in Children, measured using PedsQL 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

Timepoint [13]

Secondary outcome [14]

The difference in total cost over the treatment period relative to the difference in quality adjusted life years of the proposed treatment combinations for short intensive therapy, prolonged intensive therapy and consolidation therapy as well as for the combination of intensive therapy and consolidation therapy. Total cost between treatments calculated as the sum product of health resource utilisation and resource unit price during treatment period. This data is collected from a participant costs questionnaire and if participant consents from their hospital medical records obtained from the relevant state or territories data linkage unit, and their MBS and PBS data from the DHS.

Timepoint [14]

From date of randomization for the duration of treatment up to 56 weeks for those allocated to short intensive therapy and up to 62 weeks for those allocated to prolonged intensive therapy.

Secondary outcome [15]

The change in six minute walk distance for adult participants from the date of randomisation to up to 62 weeks according to treatment path and in participants who do and do not clear MABS at time point final.

Timepoint [15]

from date of randomisation for the duration of treatment up to 56 weeks for those allocated to short intensive treatment and up to 62 weeks for those allocated to prolonged intensive treatment.

Eligibility

Key inclusion criteria

Intervention Cohort Inclusion Criteria:
Subjects meeting all 3 ATS clinical, radiological and microbiological criteria for MABS pulmonary disease (PD) and who have confirmed MABS isolates will be eligible for randomisation into the intervention cohort. There is no minimum or maximum eligible age for participation. Subjects with mixed NTM infections (slow growers + MABS) will also be recruited as adding ethambutol will be permitted if required by the treating physician. Subjects with recurrence of MABS infection following completion of previously successful treatment will be eligible as there is strain-typing evidence that recurrence is usually associated with a new isolate.

Observation Cohort Inclusion Criteria:
Subjects who do not meet ATS criteria for MABS-PD but have a positive MABS respiratory culture, or participants who meet the criteria for MABS-PD but are not commencing MABS treatment are eligible for the observation cohort and will receive all the same outcome measures. If at a later point these participants meet the ATS criteria for MABS-PD or commence MABS treatment these subjects may be randomised into the intervention cohort.

Minimum age

No limit

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Receiving active treatment for MABS within the previous 12 months, except azithromycin for participants with cystic fibrosis and bronchiectasis.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Minimisation is a dynamic randomisation approach used in clinical trials to balance allocation to treatment arms with respect to a number of important stratification factors.

There will be three stages of randomisation in the intervention program of this study, dictating the treatment the participant will receive:
Randomisation 1: The first randomisation will be at the start of the intensive phase, with all participants randomised between the different intensive therapy arms for a period of 6 weeks.
Randomisation 2: The second randomisation will ONLY be for participants who are still MABS positive at week six. Randomisation will occur at the end of week 6 and will allocate participants to either;
1- Continue intensive therapy which will be followed by consolidation
2- Immediately commence consolidation therapy.

Randomisation 3: This randomisation will allocate participants to the consolidation therapy arms either at week 6 or at week 12 depending on the most recent MABS clearance result, i.e. from week six or (if applicable) from week 12 following prolonged intensive therapy.
Week 6: This randomisation occurs at 6 weeks for patients who have cleared MABS at 6 weeks and for patients who remained MABS positive at 6 weeks and were randomised in randomisation 2 to start consolidation.
Week 12: Patients who are randomised to prolonged intensive therapy will be randomised between the consolidation arms at the end of week 12.

Intervention cohort participants will be randomsied according to the stratification criteria below:
1- Macrolide resistance*: *Any of these measurement methods are acceptable for defining macrolide resistance (in order of preference);
a. Inducible at 14 days or constitutive at 3 days
b. Erm(41) status: Functional or dysfunctional
c. MABS subspecies: M. abscessus & M. bolletii combined or M. massiliense
2. Age: <12 years, 12-30 years and >30 years of age
3. Sex
4. Location: Australia and New Zealand as one stratum, United Kingdom and Ireland as one stratum, Denmark, France and the Netherlands as another stratum and Canada as one stratum
5. Cystic Fibrosis Status
6. Mixed NTM infections at enrolment
7. MABS positive culture (at initial randomisation to intensive therapy and for randomisation 2 all participants will have a positive culture, so this factor will not be required. However, it will be required for randomisation 3)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

For participants enrolled in the intervention cohort a respiratory sample assessing MABS will be collected at the completion of 4 weeks of intensive therapy. Intervention cohort subjects will continue intensive therapy until results are available (10-14 days). Subjects with positive cultures for MABS at this point, will be randomised 1:1 to either continuing a further 6 weeks of intensive treatment before starting consolidation or starting consolidation immediately.
When randomised to the consolidation phase subjects will be randomised 1:1 to oral azithromycin, clofazimine and doxycycline or moxifloxacin + additional IA for 46 wks to complete a total 52 or 58 wks therapy.

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

2/12/2019

Actual

2/03/2020

Date of last participant enrolment

Anticipated

31/12/2028

Actual

Date of last data collection

Anticipated

31/12/2028

Actual

Sample size

Target

300

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,WA,VIC

Recruitment hospital [1]

The Prince Charles Hospital - Chermside

Recruitment hospital [2]

Greenslopes Private Hospital - Greenslopes

Recruitment hospital [3]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [4]

Mater Adult Hospital - South Brisbane

Recruitment hospital [5]

Gold Coast University Hospital - Southport

Recruitment hospital [6]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [7]

John Hunter Hospital - New Lambton

Recruitment hospital [8]

The Children's Hospital at Westmead - Westmead

Recruitment hospital [9]

Westmead Hospital - Westmead

Recruitment hospital [10]

Sydney Children's Hospital - Randwick

Recruitment hospital [11]

The Alfred - Prahran

Recruitment hospital [12]

Concord Repatriation Hospital - Concord

Recruitment hospital [13]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [14]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [15]

Perth Children's Hospital - Nedlands

Recruitment hospital [16]

Sunshine Coast University Hospital - Birtinya

Recruitment hospital [17]

Queensland Children's Hospital - South Brisbane

Recruitment hospital [18]

Royal Perth Hospital - Perth

Recruitment hospital [19]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [20]

Queensland Children's Hospital - South Brisbane

Recruitment hospital [21]

Royal Perth Hospital - Perth

Recruitment hospital [22]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [23]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

4032 - Chermside

Recruitment postcode(s) [2]

4120 - Greenslopes

Recruitment postcode(s) [3]

4102 - Woolloongabba

Recruitment postcode(s) [4]

4215 - Southport

Recruitment postcode(s) [5]

2050 - Camperdown

Recruitment postcode(s) [6]

2305 - New Lambton

Recruitment postcode(s) [7]

2145 - Westmead

Recruitment postcode(s) [8]

2031 - Randwick

Recruitment postcode(s) [9]

3004 - Prahran

Recruitment postcode(s) [10]

2139 - Concord

Recruitment postcode(s) [11]

6009 - Nedlands

Recruitment postcode(s) [12]

5000 - Adelaide

Recruitment postcode(s) [13]

6009 - Broadway Nedlands

Recruitment postcode(s) [14]

4575 - Birtinya

Recruitment postcode(s) [15]

6000 - Perth

Recruitment postcode(s) [16]

3050 - Parkville

Recruitment postcode(s) [17]

6000 - Perth

Recruitment postcode(s) [18]

3050 - Parkville

Recruitment postcode(s) [19]

3050 - Parkville

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Christchurch

Country [2]

New Zealand

State/province [2]

Auckland

Country [3]

United Kingdom

State/province [3]

Nottingham

Country [4]

United Kingdom

State/province [4]

London

Country [5]

Ireland

State/province [5]

Dublin

Country [6]

Netherlands

State/province [6]

Rotterdam

Country [7]

Denmark

State/province [7]

Copenhagen

Country [8]

Singapore

State/province [8]

Singapore

Country [9]

Israel

State/province [9]

Country [10]

Brazil

State/province [10]

Country [11]

Taiwan, Province Of China

State/province [11]

Country [12]

Portugal

State/province [12]

Country [13]

France

State/province [13]

Country [14]

Singapore

State/province [14]

Singapore

Country [15]

Israel

State/province [15]

Country [16]

Brazil

State/province [16]

Country [17]

Taiwan, Province Of China

State/province [17]

Country [18]

Portugal

State/province [18]

Country [19]

France

State/province [19]

Country [20]

France

State/province [20]

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

The Commonwealth of Australian represented by Department of Health

Address [1]

23 Furzer Street Woden
ACT 2606

Country [1]

Australia

Funding source category [2]

Other

Name [2]

Anonymous donor

Address [2]

N/K

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

Cystic Fibrosis Foundation

Address [3]

4550 Montgomery Ave.
Suite 1100 N
Bethesda, MD 20814

Country [3]

United States of America

Funding source category [4]

University

Name [4]

The Unviersity of Queensland

Address [4]

The University of Queensland
Brisbane QLD 4072 Australia

Country [4]

Australia

Funding source category [5]

Charities/Societies/Foundations

Name [5]

Children's Hospital Foundation

Address [5]

494 Stanley Street, South Brisbane QLD 4101

Country [5]

Australia

Primary sponsor type

University

Name

The University of Queensland

Address

Office of Sponsored Research
The University of Queensland
Cumbrae Stewart Building 72
Research Road, QLD 4072

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Children’s Health Queensland Human Research Ethics Committee

Ethics committee address [1]

Level 7, Centre for Children’s Health Research
Lady Cilento Children’s Hospital Precinct,
62 Graham Street
South Brisbane QLD 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/09/2019

Approval date [1]

10/10/2019

Ethics approval number [1]

Ethics committee name [2]

Metro North Health Human Research Ethics Committee

Ethics committee address [2]

Level 7, Block 7, RBWH Campus
Herson, QLD, 4029

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

22/08/2019

Approval date [2]

26/08/2019

Ethics approval number [2]

Summary

Brief summary

Mycobacterium abscessus (MABS) is a group of rapid-growing, multi-drug resistant non-tuberculous mycobacteria causing infections in humans. While the overall numbers affected is small, the prevalence of infections is increasing. Individuals with cystic fibrosis (CF) and bronchiectasis are at particular risk of MABS becoming established within their lungs, resulting in a clinical spectrum ranging from simple colonisation to severe infection with increased healthcare utilisation and mortality. There is no evidence for either the timing of starting therapy, or for the currently used treatment regimens, which are complex, often poorly tolerated, and involve multiple expensive and toxic drug combinations given for at least 1-2 years. These considerable challenges have resulted in very few clinical trials being performed leaving an urgent clinical management evidence vacuum.
Population: Those with MABS positive respiratory samples.
Intervention: We aim to build an iterative, experimental clinical trial platform with adaptive properties and an observation arm to enable multiple treatment combinations to be evaluated in patients with and without CF, in those infected with different MABS subspecies, and strains with macrolide resistance. The platform will enable future novel treatments to efficiently enter the trial as they become available.
Comparison: The trial platform will include the current standard of care as a comparator arm; as evidence is accumulated new comparators may be incorporated.
Outcome: The trial platform will facilitate the evolution of optimal management for MABS lung disease with primary outcome of microbial clearance and include pharmacokinetic and health economic evaluation. Biomarkers will be developed to guide when to initiate treatment, and enable the monitoring of treatment responses. This will reduce unnecessary treatment associated toxicity and costs and enable targeted therapeutic approaches to maximise clinical benefit.

Trial website

FORMaTtrial.com

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Claire Wainwright

Address

Centre for Children's Health Research
Level 7, 62 Graham Street
Lady Cilento Children's Hospital Precinct
South Brisbane QLD 4101

Country

Australia

Phone

+617 30681111

Fax

+617 30697159

[email protected]

Contact person for public queries

Name

Prof Claire Wainwright

Address

Centre for Children's Health Research
Level 7, 62 Graham Street
Lady Cilento Children's Hospital Precinct
South Brisbane QLD 4101

Country

Australia

Phone

+617 30681111

Fax

+617 30697159

[email protected]

Contact person for scientific queries

Name

Prof Claire Wainwright

Address

Centre for Children's Health Research
Level 7, 62 Graham Street
Lady Cilento Children's Hospital Precinct
South Brisbane QLD 4101

Country

Australia

Phone

+617 30681111

Fax

+617 30697159

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All de-identified raw data measured during the trial will be made available.

When will data be available (start and end dates)?

Immediately following publication with no end date.

Available to whom?

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

Available for what types of analyses?

Any purpose.

How or where can data be obtained?

Upon the approval for data sharing by Professor Claire Wainwright the requester will be required to sign a data agreement.

What supporting documents are/will be available?

Doc. No.	Type	Email	Other Details	Attachment
5868	Ethical approval			374430-(Uploaded-30-10-2019-10-43-11)-Study-related document.pdf
5869	Informed consent form	[email protected]
5870	Other		Attachments 1: Paediatric and adult drug dosing ta... [More Details]	374430-(Uploaded-07-08-2023-13-48-42)-Study-related document.docx
5871	Other		Attachment 2: Paediatric and adult drug dosing ta... [More Details]	374430-(Uploaded-07-08-2023-13-54-04)-Study-related document.docx
5872	Study protocol	[email protected]
20560	Study protocol			374430-(Uploaded-04-08-2023-16-16-18)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Pulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline.	2019	https://dx.doi.org/10.1111/jpc.14427

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically