About the Trial

What is FORMaT?

FORMaT is an adaptive, multi-arm, platform clinical trial designed to find out which combination of medications best treat Mycobacterium abscessus (MABS) lung infections. The treatment of MABS lung infections is complicated and patients are required to take multiple medications which are often poorly tolerated and can cause toxic side effects.

The combination of medications used to treat MABS chest infections are also very expensive and the choice of antibiotics used is based on the experience of doctors as there is very limited scientific evidence for what medication combinations should be used. When to start these medications is also not well understood. As a result, the FORMaT trial has been designed as an adaptive, multi-arm, platform clinical trial and brings together internationally recognized experts and clinical leaders to solve this treatment challenge.

What is an adaptive, multi-arm, platform clinical trial?

The FORMaT trial has been developed using an adaptive, platform clinical trial design. The trial platform provides a framework that can be used to continuously evaluate different treatment protocols. Initially, the design of the FORMaT trial evalulates the standard medications prescribed to treat MABS lung disease as these standard medications have not been properly tested for treating this disease in a clinical trial (Figure 1).

The trial platform can also add new treatment arms into the trial as well as having the ability to remove any treatment arms deemed ineffective or too toxic. The adaptive part of the trial allows the data to be analysed while the trial is ongoing and these results can be used to change the trial design in real-time. This means that we can quickly identify effective treatment arms and potentially allocate more people to the successful treatment arm/s.

Overall, the FORMaT trial is designed to find effective treatment solutions to treat MABS lung disease.

The FORMaT Trial consists of two participant groups:

Intervention Group: Participants that meet the criteria for treatment of MABS lung disease and require medications to treat their MABS lung disease.
Observation Group: Participants that do not meet the criteria for treatment of MABS lung disease or have chosen not to take the medications.

For those participants who will be treated (the Intervention group), our specially designed FORMaT database will randomise (allocate by chance) each participant into an intervention arm depending on a number of clinical factors. There are three intervention arms which have a “base” medication combination that is shared between all intervention arms.

One intervention arm is a reference arm and the remaining two intervention arms use the same base medication combination used in the control arm along with repurposed medication added to each intervention arm.

Figure 1: FORMaT trial flow diagram. Eligibility into the intervention program is determined at screening. At randomisation 1 (▲); participants are randomised between the different intensive therapy arms (Intensive A, Intensive B and Intensive C) for a period of 6 weeks. At the end of intensive therapy, it will be determined if participants are still MABS positive, or MABS negative (cleared). Randomisation 2 (★) will ONLY be for participants who are still MABS positive at week 6 and will allocate participants to either 1) continue intensive therapy for a further 6 weeks or 2) immediately commence consolidation therapy. Randomisation 3 (✢) allocates participants to the consolidation therapy arms (consolidation arm a or arm b) either at week 6 or at week 12 depending on MABS clearance at the end of week 6 and randomisation 2 (if relevant). This figure demonstrates the capacity to add future intensive and consolidation arms.

FORMaT Intervention Program Treatment Regimens

Intensive Arm A	Intensive Arm B	Intensive Arm C
1. IV amikacin, and; 2. IV tigecycline, and; 3. IV imipenem OR IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin, and; 5. Oral Clofazimine	1. Inhaled amikacin, and; 2. IV tigecycline, and; 3. IV imipenem OR IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin, and; 5. Oral Clofazimine	1. IV amikacin, and; 2. IV tigecycline, and; 3. IV imipenem OR IV cefoxitin, and; 4. Oral azithromycin OR Oral clarithromycin

Ethambutol may also be added to the treatment arms for participants with confirmed mixed NTM infections (slow growers + MABS) if required by the treating physician.
N.B. The intravenous preparation of amikacin is to be given via inhalation in Intensive Arm B. A low preservative intravenous amikacin preparation is recommended.

Consolidation Arm A	Consolidation Arm B
	1. Inhaled amikacin (IV preparation, NOT liposomal amikacin)
1. Oral clofazimine	2. Oral clofazimine
2. Oral azithromycin OR Oral clarithromycin, and;	3. Oral azithromycin OR Oral clarithromycin, and;
3. In combination with one to three of the following oral antibiotics: o Oral linezolid o Oral trimethoprim/sulfamethoxazole (co-trimoxazole) o Oral doxycycline o Oral moxifloxacin o Oral bedaquiline o Oral rifabutin	4. In combination with one to three of the following oral antibiotics: o Oral linezolid o Oral trimethoprim/sulfamethoxazole (co-trimoxazole) o Oral doxycycline o Oral moxifloxacin o Oral bedaquiline o Oral rifabutin

Ethambutol may also be added to the treatment arms for participants with confirmed mixed NTM infections (slow growers + MABS) if required by the treating physician.

Trial Registration

The FORMaT Trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), ClinicalTrials.gov and ISRCTN – The UK’s Clinical Study Registry: