Mycobacterium Abscessus Pulmonary DiseasePhase 2FORMaT-EVOLVENCT07485010
Testing a Novel Combination Treatment (Arm D) Versus Standard of Care for Intensive Phase Treatment for Mycobacterium Abscessus Pulmonary Disease in People With or Without Cystic Fibrosis in the Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT) Adaptive Platform Trial
A Phase 2 study testing Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours), Ceftriaxone for Injection and Amoxicillin in people with Mycobacterium Abscessus Pulmonary Disease and Mycobacterium Abscessus Infection, run by The University of Queensland.
Trial summary
The goal of this clinical trial is to learn if a new combination antibiotic treatment (Arm D) works to treat a rare lung condition called mycobacterium abscessus pulmonary disease in people of any age and sex, when compared to the standard treatments. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Mycobacterium Abscessus Pulmonary Disease, Mycobacterium Abscessus Infection, Non-Tuberculous Mycobacterial (NTM) Infections
- What is being tested?
- Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours), Ceftriaxone for Injection and Amoxicillin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- Apr 2027to Jul 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Must meet eligibility criteria as per the FORMaT Master Protocol and Appendix A1 Inclusion Criteria (NCT04310930).
- Male or female participants aged 12 years and older.
Who cannot join
- Must not have any exclusion criteria as per the FORMaT Master Protocol and Appendix A1 Exclusion Criteria (NCT04310930).
- Participants aged <12 years old.
- Participants aged between 12 and <18years old with clinically significant renal impairment as indicated by an age-appropriate estimated creatinine clearance.
- Known hypersensitivity to any of the therapies for which no alternative option(s) have been provided. This includes:
- Sulbactam/durlobactam
- Ceftriaxone,
Show all 9Show fewer
- Amoxicillin,
- Macrolide antibiotics, and
- Clofazimine.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Multi-centre, Randomised Trial Comparing a Novel Combination Treatment (Arm D - Intravenous Sulbactam-durlobactam in Combination With Intravenous Ceftriaxone, Oral Amoxicillin, Oral Azithromycin and Oral Clofazimine) Versus Standard of Care Treatments for the Intensive Phase of Treatment for Mycobacterium Abscessus Pulmonary Disease in People With or Without Cystic Fibrosis in the Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT) Adaptive Platform Trial
The goal of this clinical trial is to learn if a new combination antibiotic treatment (Arm D) works to treat a rare lung condition called mycobacterium abscessus pulmonary disease in people of any age and sex, when compared to the standard treatments. It will also learn about the safety of this new combination antibiotic treatment when compared to the standard treatments. The main questions it aims to answer are:
- How well does Arm D treat mycobacterium abscessus pulmonary disease?
- What side effects does Arm D cause when used to treat mycobacterium abscessus pulmonary disease? Researchers will compare Arm D to the current standard of care treatments to see if Arm D treats mycobacterium abscessus pulmonary disease better and if it will cause less side effects.
Read more
Participants will:
- Be screened and recruited to the FORMaT adaptive platform trial (NCT04310930)
- Be given Arm D for 4 weeks or standard of care treatments for 6 weeks.
- Be reviewed by the study doctors weekly for checkups and tests.
- Provide respiratory samples (sample coughed up from the chest), respond to quality-of-life questionnaires, have CT lung scans and blood tests.
Read the detailed description
Mycobacterium abscessus pulmonary disease (MABS-PD) is a rare and serious lung infection that affects people who already have lung problems such as bronchiectasis, cystic fibrosis, past tuberculosis, or weakened immune systems, as well as people who do not have pre-existing lung problems. This infection is becoming more common worldwide and is difficult to treat because it is highly resistant to many antibiotics. Current treatment usually lasts 12-18 months, is hard for patients to tolerate, and often causes significant side effects.
This study will test a new combination of antibiotics given during the first four weeks of treatment-the "intensive phase." The new regimen includes intravenous sulbactam-durlobactam and intravenous ceftriaxone, along with oral amoxicillin, oral azithromycin, and oral clofazimine. The trial will compare this new approach to the current standard-of-care therapy using the existing FORMaT adaptive platform trial, which was created to identify better treatments for MABS-PD.
The main goal of the study is to find out whether the new combination can clear the infection while also being easier for patients to tolerate. Additional study measures will look at lung function, chest imaging, quality of life, and health-care use. The trial also includes several research components that will examine how the drugs behave in the body, immune responses, mycobacterial genetics, and antibiotic resistance.
This innovative study aims to provide the first high-quality clinical evidence for a potentially more effective and less toxic treatment option for people living with this challenging and severe lung infection.
- Conditions
- Mycobacterium Abscessus Pulmonary Disease, Mycobacterium Abscessus Infection, Non-Tuberculous Mycobacterial (NTM) Infections, Non-Tuberculous Mycobacteria Pulmonary Disease
- Being tested
- Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours), Ceftriaxone for Injection, Amoxicillin, Azithromcyin, clarithromycin
- Keywords
- adaptive platform trial, dual beta lactam, sulbactam-durlobactam
- Medical subject headings
- Mycobacterium Infections, Nontuberculous, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)Drug
Adults and Children 12 years and older: IV sulbactam/durlobactam Greater than or equal to 130ml/min Every FOUR (4) hourly. Administered by intravenous infusion over 3 hours.
For CrCL 45 to 129ml/min 1g sulbactam/ 1g durlobactam Every SIX (6) hourly. Administer by intravenous infusion over 3 hours.
For CrCL 30 to 44ml/min
1g sulbactam/ 1g durlobactam Every EIGHT (8) hourly. Administer by intravenous infusion over 3 hours.
For CrCL 15 to 29ml/min 1g sulbactam/ 1g durlobactam Every TWELVE (12) hourly. Administer by intravenous infusion over 3 hours.
For CrCL<15ml/min
1g sulbactam/ 1g durlobactam Every TWELVE (12) hourly for first 3 doses then reduce to every 24 hourly thereafter. Administer by intravenous infusion over 3 hours.
Ceftriaxone for InjectionDrug
Adults and Children 12 years and older: IV ceftriaxone
1g Every TWELVE (12) hourly
AmoxicillinDrug
Adults and Children 12 years and older: Oral amoxicillin 1000mg Three times daily
AzithromcyinDrug
Adults and Children 12 years and older: Oral Azithromycin 250 - 500mg Once daily If <40kg or poorly tolerated 250mg Once daily
clarithromycinDrug
Oral clarithromycin. Only for use if azithromycin not tolerated. Adults: 500mg twice daily. Children: 12-18 years of age: Dosing independent of weight 500mg twice daily
ClofazimineDrug
Adults and Children 12 years and older: Oral clofazimine 100mg to 300mg Once daily
EthambutolDrug
For participants with confirmed mixed NTM (slow growers + MABS) infections, there is an option to add oral ethambutol to the treatment arm in accordance with the dosing below.
Oral ethambutol 15mg/kg (rounded to account for tablet strength) OR Once daily 25mg/kg (rounded to account for tablet strength) Thrice weekly
Amikacin InjectionDrug
Adults: Intravenous amikacin 5mg/kg once daily or 7.5mg/kg twice daily or 20-25 mg/kg thrice weekly. Children: Intravenous amikacin 15-30 mg/kg once daily, maximum dose 1500mg
tigecyclineDrug
Adults: Intravenous Tigecycline 25 mg increasing by 5 mg every two doses until either maximum dose reached (50mg) or until patient is unable to tolerate twice daily. Children (≥8 years of age) intravenous tigecycline: Day 1- 0.6mg/kg twice daily to a maximum of 25mg. Day 2- 0.6mg/kg (maximum 25mg) in the morning, 1.2 mg/kg (maximum 50mg) at night. Day 3- 1.2mg/kg (maximum 50 mg) twice daily
Imipenem + CilastatinDrug
Adults: Intravenous Imipenem (≥50kg) 500mg twice daily (<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated).
CefoxitinDrug
Adults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily.
Amikacin (Inhalation)Drug
Adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily. PLEASE NOTE: low preservative intravenous amikacin preparation to be used as inhalation, NOT liposomal amikacin.
linezolidDrug
Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily.
Children: >12 years 600mg once daily.
Trimethoprim / SulfamethoxazoleDrug
Adults and children 12 years and older: Oral Co-trimoxazole (Trimethoprim / Sulfamethoxazole) 160/800mg twice daily.
DoxycyclineDrug
Adults and Children 12 years and older: Oral doxycycline 100mg once daily.
moxifloxacinDrug
Adult: Oral moxifloxacin 400mg once daily. Children 12 years and older: Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg
bedaquilineDrug
Adult: Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months).
RifabutinDrug
Adult: Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children 12 years and older: Oral rifabutin 5mg/kg once daily
| Study group | Role | What they receive |
|---|---|---|
| Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen | Experimental | Weeks 1 to 4 (and Weeks 7 to 10 if randomised to Prolonged Intensive)
1. IV sulbactam-durlobactam
2. IV ceftriaxone
3. Oral amoxicillin
4. Oral azithromycin or clarithromycin
5. Oral clofazimine. Weeks 5 to 6 (and Weeks 8 to 12 if randomised to Prolonged Intensive)
1. Oral clofazimine, and; 2. Oral azithromycin or clarithromycin, and; 3. In combination with one to three of the following oral antibiotics guided by participant susceptibility and tolerance:
* Linezolid,
* Trimethoprim / sulfamethoxazole (co-trimoxazole),
* Bedaquiline,
* Rifabutin,
* Doxycycline,
* Moxifloxacin. Receives: Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours); Drug: Ceftriaxone for Injection; Drug: Amoxicillin; Drug: Azithromcyin; Drug: clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: linezolid; Drug: Trimethoprim / Sulfamethoxazole; Drug: Doxycycline; Drug: moxifloxacin; Drug: bedaquiline; Drug: Rifabutin |
| Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine | Active comparator | 1. IV amikacin, and;
2. IV tigecycline, and;
3. IV imipenem/cilastatin or IV cefoxitin, and;
4. Oral azithromycin or oral clarithromycin, and;
5. Oral clofazimine. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. Receives: Drug: Azithromcyin; Drug: clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: Amikacin Injection; Drug: tigecycline; Drug: Imipenem + Cilastatin; Drug: Cefoxitin |
| Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine | Experimental | 1. Inhaled amikacin, and;
2. IV tigecycline, and;
3. IV imipenem/cilastatin or IV cefoxitin, and;
4. Oral azithromycin or oral clarithromycin, and;
5. Oral clofazimine. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. Receives: Drug: Azithromcyin; Drug: clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: tigecycline; Drug: Imipenem + Cilastatin; Drug: Cefoxitin; Drug: Amikacin (Inhalation) |
| Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide | Experimental | 1. IV amikacin, and;
2. IV tigecycline, and;
3. IV imipenem/cilastatin or IV cefoxitin, and;
4. Oral azithromycin or oral clarithromycin. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. Receives: Drug: Azithromcyin; Drug: clarithromycin; Drug: Ethambutol; Drug: Amikacin Injection; Drug: tigecycline; Drug: Imipenem + Cilastatin; Drug: Cefoxitin |
| Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents | 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. For 46 weeks after completion of Intensive Therapy phase. Receives: Drug: Azithromcyin; Drug: clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: linezolid; Drug: Trimethoprim / Sulfamethoxazole; Drug: Doxycycline; Drug: moxifloxacin; Drug: bedaquiline; Drug: Rifabutin |
| Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents | 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. For 46 weeks after completion of Intensive Therapy phase. Receives: Drug: Azithromcyin; Drug: clarithromycin; Drug: Clofazimine; Drug: Ethambutol; Drug: Amikacin (Inhalation); Drug: linezolid; Drug: Trimethoprim / Sulfamethoxazole; Drug: Doxycycline; Drug: moxifloxacin; Drug: bedaquiline; Drug: Rifabutin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome of the Intervention Program is microbiological clearance of Mycobacterium abscessus (MABS) with good tolerance of the interventions.
Definition of MABS clearance at final outcome:
Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation.
Definition of tolerance:
Tolerance is based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug will be assessed in the determination of tolerance. "Good" tolerance is defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" tolerance is defined as any adverse events attributed as possibly-, probably-, or definitely-related to study drug coded as CTCAE grades 3, 4, or 5.
Measured: Screening (Day 0) to End of treatment plus four weeks off-treatment (Final Outcome Visit (Week 56 for those allocated to Immediate Consolidation or Week 62 for those allocated to Prolonged Intensive).
Nested Study A3.1 Type of Short Intensive Therapy - MABS clearance from respiratory sample(s) with tolerance.
Microbiological clearance of MABS from respiratory samples collected at 4 weeks with good tolerability assessed at the end of short intensive therapy between Arm D and the standard of care arms 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. Treatment tolerance is defined as no Treatment emergent adverse events and/or Treatment emergent adverse events that are "possibly-", "probably-", or "definitely-" related to study drug and coded as grade 1 or 2 based on the CTCAEv5.0.
Measured: Screening (Day 0) to the End of Short Intensive Therapy (Week 6).
Nested Study A3.2 - Duration of intensive therapy for patients completing short intensive treatment with ongoing positive MABS cultures collected at 4 weeks and randomised to either a further 6 weeks intensive therapy or immediate consolidation.
To compare the microbiological clearance from samples collected at 10 weeks with good tolerability between those who are allocated to prolonged intensive therapy and those allocated to immediate consolidation following short intensive therapy.
MABS clearance, assessed at the end of prolonged intensive therapy (for those allocated to prolonged intensive) or at 12 weeks (for those allocated to immediate consolidation) will be defined as negative MABS cultures from all 3 sputum samples or from one BAL sample collected at 10 weeks. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
Measured: Screening (Day 0) to EITHER the End of Prolonged Intensive Therapy (for those allocated to Prolonged Intensive) OR Week 12 Visit (for those allocated to immediate consolidation therapy).
Secondary outcomes (16)
Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway.
Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway. Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation.
Measured: Screening (Day 0); at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Incidence of Treatment emergent adverse events
Safety of treatment combinations based on the reporting of adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drugs.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Safety of treatments based on changes in microbiological resistance.
Safety of treatments based on changes to microbiological resistance of the MABS bacteria during the study treatment period.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in Forced Expiratory Volume in 1 second (FEV1) z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome.
Change in FEV1 z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Phenotype of the structural abnormalities of chest Computer Tomography (CT) and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome.
Phenotype of the structural abnormalities of chest CTs and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome.
Measured: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment.
Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment.
Measured: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Cystic Fibrosis Questionnaire - Respiratory domain (CFQ-R)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the CFQ-R) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. CFQ-R is the Cystic Fibrosis Questionnaire Revised and will be completed by all CF participants. The CFQ-R has a score from 0 to 100. With 0 indicating the lowest quality of life and 100 indicating the highest.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the EuroQol 5-Dimension (EQ-5D)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the EQ-5D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. EQ-5D is the EuroQol 5 Dimensions and will be completed by all participants.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the St George's Respiratory Questionnaire (SGRQ)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the SGRQ) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. SGRQ is the St George's Respiratory Questionnaire and will be completed by all non-CF participants who are 18 years and older.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Short Form (SF-36)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the SF-36) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. The SF-36 is the Short-Form 36 questionnaire and will be completed by all participants 16 years and older. The SF-36 operates on a transformed scoring system ranging from 0 (lowest/worst health) to 100 (highest/best health). Lowest Score (0): Represents maximum disability, poor health, or significant limitation. Highest Score (100): Represents no disability, optimal health, and no limitations.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Pediatric Quality of Life Inventory (PedsQL)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the PedsQL) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. The PedsQL is the Pediatric Quality of Life Inventory questionnaire and will be completed by participants 2 years old to 16 years old. The PedsQL responses are transformed onto a 0 to 100 scale, where a higher score indicates a better Health-Related Quality of Life (HRQOL). Lowest Score: 0 (indicates poorest quality of life/most problems). Highest Score: 100 (indicates best quality of life/no problems).
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Child Health Utility 9 Dimensions (CHU-9D)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Change in HRQoL (measured using the CHU-9D) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. CHU-9D is the Child Health Utility 9D and will be completed by all children aged 7 to 17 years of age.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Cost effectiveness of the treatment combinations (measured using the Costs Questionnaire across intensive and consolidation phases of the trial.
Cost effectiveness of the treatment combinations across intensive and consolidation phases of the trial. Cost effectiveness of the treatments will be assessed using the unvalidated "Costs Questionnaire".
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Cost effectiveness of the treatment combinations (measured using Linked Administrative Healthcare Utilisation Data (for applicable jurisdictions)) across intensive and consolidation phases of the trial.
Cost effectiveness of the treatment combinations across intensive and consolidation phases of the trial. Cost effectiveness of the treatments will be assessed the linked administrative healthcare utilisation data e.g. in Australian participants.
Measured: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Causes for early withdrawal from MABS-PD treatment due to reasons other than poor tolerance as defined in the primary objectives.
Causes for early withdrawal from MABS-PD treatment due to reasons other than poor tolerance as defined in the primary objectives.
Measured: At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2026
- Study startApr 2027 (estimated)
- Primary completionApr 2031 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mycobacterium Abscessus Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Queensland
- Sponsor type
- University, hospital or other
- Collaborators
- Innoviva Specialty Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07485010
- Sponsor's protocol ID
- FORMaT002
- Acronym
- FORMaT-EVOLVE
- Status last verified
- Mar 2026
- First submitted
- 12 Mar 2026
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Randomised Trial Comparing a Novel Combination Treatment (Arm D - Intravenous Sulbactam-durlobactam in Combination With Intravenous Ceftriaxone, Oral Amoxicillin, Oral Azithromycin and Oral Clofazimine) Versus Standard of Care Treatments for the Intensive Phase of Treatment for Mycobacterium Abscessus Pulmonary Disease in People With or Without Cystic Fibrosis in the Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT) Adaptive Platform Trial
- ClinicalTrials.gov ID
- NCT07485010
- Acronym / sponsor ID
- FORMaT-EVOLVE / FORMaT002
- Conditions
- Mycobacterium Abscessus Pulmonary Disease, Mycobacterium Abscessus Infection, Non-Tuberculous Mycobacterial (NTM) Infections, Non-Tuberculous Mycobacteria Pulmonary Disease
- Keywords
- adaptive platform trial, dual beta lactam, sulbactam-durlobactam
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- The University of QueenslandUniversity, hospital or other
- Collaborators
- Innoviva Specialty Therapeutics
- Study start
- Apr 2027 (estimated)
- Primary completion
- Apr 2031 (estimated)
- Study completion
- Jul 2031 (estimated)
- First posted
- 20 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if a new combination antibiotic treatment (Arm D) works to treat a rare lung condition called mycobacterium abscessus pulmonary disease in people of any age and sex, when compared to the standard treatments. It will also learn about the safety of this new combination antibiotic treatment when compared to the standard treatments. The main questions it aims to answer are:
- How well does Arm D treat mycobacterium abscessus pulmonary disease?
- What side effects does Arm D cause when used to treat mycobacterium abscessus pulmonary disease? Researchers will compare Arm D to the current standard of care treatments to see if Arm D treats mycobacterium abscessus pulmonary disease better and if it will cause less side effects.
Participants will:
- Be screened and recruited to the FORMaT adaptive platform trial (NCT04310930)
- Be given Arm D for 4 weeks or standard of care treatments for 6 weeks.
- Be reviewed by the study doctors weekly for checkups and tests.
- Provide respiratory samples (sample coughed up from the chest), respond to quality-of-life questionnaires, have CT lung scans and blood tests.
Detailed description
Mycobacterium abscessus pulmonary disease (MABS-PD) is a rare and serious lung infection that affects people who already have lung problems such as bronchiectasis, cystic fibrosis, past tuberculosis, or weakened immune systems, as well as people who do not have pre-existing lung problems. This infection is becoming more common worldwide and is difficult to treat because it is highly resistant to many antibiotics. Current treatment usually lasts 12-18 months, is hard for patients to tolerate, and often causes significant side effects.
This study will test a new combination of antibiotics given during the first four weeks of treatment-the "intensive phase." The new regimen includes intravenous sulbactam-durlobactam and intravenous ceftriaxone, along with oral amoxicillin, oral azithromycin, and oral clofazimine. The trial will compare this new approach to the current standard-of-care therapy using the existing FORMaT adaptive platform trial, which was created to identify better treatments for MABS-PD.
The main goal of the study is to find out whether the new combination can clear the infection while also being easier for patients to tolerate. Additional study measures will look at lung function, chest imaging, quality of life, and health-care use. The trial also includes several research components that will examine how the drugs behave in the body, immune responses, mycobacterial genetics, and antibiotic resistance.
This innovative study aims to provide the first high-quality clinical evidence for a potentially more effective and less toxic treatment option for people living with this challenging and severe lung infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen | Experimental | Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours), Drug: Ceftriaxone for Injection, Drug: Amoxicillin, Drug: Azithromcyin, Drug: clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: linezolid, Drug: Trimethoprim / Sulfamethoxazole, Drug: Doxycycline, Drug: moxifloxacin, Drug: bedaquiline, Drug: RifabutinWeeks 1 to 4 (and Weeks 7 to 10 if randomised to Prolonged Intensive) 1. IV sulbactam-durlobactam 2. IV ceftriaxone 3. Oral amoxicillin 4. Oral azithromycin or clarithromycin 5. Oral clofazimine. Weeks 5 to 6 (and Weeks 8 to 12 if randomised to Prolonged Intensive) 1. Oral clofazimine, and; 2. Oral azithromycin or clarithromycin, and; 3. In combination with one to three of the following oral antibiotics guided by participant susceptibility and tolerance: * Linezolid, * Trimethoprim / sulfamethoxazole (co-trimoxazole), * Bedaquiline, * Rifabutin, * Doxycycline, * Moxifloxacin. |
| Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine | Active comparator | Drug: Azithromcyin, Drug: clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: Amikacin Injection, Drug: tigecycline, Drug: Imipenem + Cilastatin, Drug: Cefoxitin1. IV amikacin, and; 2. IV tigecycline, and; 3. IV imipenem/cilastatin or IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin, and; 5. Oral clofazimine. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. |
| Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine | Experimental | Drug: Azithromcyin, Drug: clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: tigecycline, Drug: Imipenem + Cilastatin, Drug: Cefoxitin, Drug: Amikacin (Inhalation)1. Inhaled amikacin, and; 2. IV tigecycline, and; 3. IV imipenem/cilastatin or IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin, and; 5. Oral clofazimine. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. |
| Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide | Experimental | Drug: Azithromcyin, Drug: clarithromycin, Drug: Ethambutol, Drug: Amikacin Injection, Drug: tigecycline, Drug: Imipenem + Cilastatin, Drug: Cefoxitin1. IV amikacin, and; 2. IV tigecycline, and; 3. IV imipenem/cilastatin or IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. |
| Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents | Active comparator | Drug: Azithromcyin, Drug: clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: linezolid, Drug: Trimethoprim / Sulfamethoxazole, Drug: Doxycycline, Drug: moxifloxacin, Drug: bedaquiline, Drug: RifabutinOral clofazimine + oral azithromycin/oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin. For 46 weeks after completion of Intensive Therapy phase. |
| Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents | Experimental | Drug: Azithromcyin, Drug: clarithromycin, Drug: Clofazimine, Drug: Ethambutol, Drug: Amikacin (Inhalation), Drug: linezolid, Drug: Trimethoprim / Sulfamethoxazole, Drug: Doxycycline, Drug: moxifloxacin, Drug: bedaquiline, Drug: RifabutinInhaled amikacin (IA), oral clofazimine + oral azithromycin/oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin. For 46 weeks after completion of Intensive Therapy phase. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Must meet eligibility criteria as per the FORMaT Master Protocol and Appendix A1 Inclusion Criteria (NCT04310930).
- Male or female participants aged 12 years and older.
Key exclusion criteria (9 listed)
- Must not have any exclusion criteria as per the FORMaT Master Protocol and Appendix A1 Exclusion Criteria (NCT04310930).
- Participants aged <12 years old.
- Participants aged between 12 and <18years old with clinically significant renal impairment as indicated by an age-appropriate estimated creatinine clearance.
- Known hypersensitivity to any of the therapies for which no alternative option(s) have been provided. This includes:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)Adults and Children 12 years and older: IV sulbactam/durlobactam Greater than or equal to 130ml/min Every FOUR (4) hourly. Administered by intravenous infusion over 3 hours. For CrCL 45 to 129ml/min 1g sulbactam/ 1g durlobactam Every SIX (6) hourly. Administer by intravenous infusion over 3 hours. For CrCL 30 to 44ml/min 1g sulbactam/ 1g durlobactam Every EIGHT (8) hourly. Administer by intravenous infusion over 3 hours. For CrCL 15 to 29ml/min 1g sulbactam/ 1g durlobactam Every TWELVE (12) hourly. Administer by intravenous infusion over 3 hours. For CrCL<15ml/min 1g sulbactam/ 1g durlobactam Every TWELVE (12) hourly for first 3 doses then reduce to every 24 hourly thereafter. Administer by intravenous infusion over 3 hours. | Drug | Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| Ceftriaxone for InjectionAdults and Children 12 years and older: IV ceftriaxone 1g Every TWELVE (12) hourly | Drug | Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| AmoxicillinAdults and Children 12 years and older: Oral amoxicillin 1000mg Three times daily | Drug | Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| AzithromcyinAdults and Children 12 years and older: Oral Azithromycin 250 - 500mg Once daily If <40kg or poorly tolerated 250mg Once daily | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| clarithromycinOral clarithromycin. Only for use if azithromycin not tolerated. Adults: 500mg twice daily. Children: 12-18 years of age: Dosing independent of weight 500mg twice daily | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| ClofazimineAdults and Children 12 years and older: Oral clofazimine 100mg to 300mg Once daily | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| EthambutolFor participants with confirmed mixed NTM (slow growers + MABS) infections, there is an option to add oral ethambutol to the treatment arm in accordance with the dosing below. Oral ethambutol 15mg/kg (rounded to account for tablet strength) OR Once daily 25mg/kg (rounded to account for tablet strength) Thrice weekly | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| Amikacin InjectionAdults: Intravenous amikacin 5mg/kg once daily or 7.5mg/kg twice daily or 20-25 mg/kg thrice weekly. Children: Intravenous amikacin 15-30 mg/kg once daily, maximum dose 1500mg | Drug | Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide |
| tigecyclineAdults: Intravenous Tigecycline 25 mg increasing by 5 mg every two doses until either maximum dose reached (50mg) or until patient is unable to tolerate twice daily. Children (≥8 years of age) intravenous tigecycline: Day 1- 0.6mg/kg twice daily to a maximum of 25mg. Day 2- 0.6mg/kg (maximum 25mg) in the morning, 1.2 mg/kg (maximum 50mg) at night. Day 3- 1.2mg/kg (maximum 50 mg) twice daily | Drug | Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide |
| Imipenem + CilastatinAdults: Intravenous Imipenem (≥50kg) 500mg twice daily (<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated). | Drug | Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide |
| CefoxitinAdults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily. | Drug | Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine, Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide |
| Amikacin (Inhalation)Adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily. PLEASE NOTE: low preservative intravenous amikacin preparation to be used as inhalation, NOT liposomal amikacin. | Drug | Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine |
| linezolidAdult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily. Children: >12 years 600mg once daily. | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| Trimethoprim / SulfamethoxazoleAdults and children 12 years and older: Oral Co-trimoxazole (Trimethoprim / Sulfamethoxazole) 160/800mg twice daily. | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| DoxycyclineAdults and Children 12 years and older: Oral doxycycline 100mg once daily. | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| moxifloxacinAdult: Oral moxifloxacin 400mg once daily. Children 12 years and older: Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| bedaquilineAdult: Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months). | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
| RifabutinAdult: Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children 12 years and older: Oral rifabutin 5mg/kg once daily | Drug | Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents, Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents, Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen |
Primary outcome
The primary outcome of the Intervention Program is microbiological clearance of Mycobacterium abscessus (MABS) with good tolerance of the interventions.
Time frame: Screening (Day 0) to End of treatment plus four weeks off-treatment (Final Outcome Visit (Week 56 for those allocated to Immediate Consolidation or Week 62 for those allocated to Prolonged Intensive).
Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation. Definition of tolerance: Tolerance is based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug will be assessed in the determination of tolerance. "Good" tolerance is defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" tolerance is defined as any adverse events attributed as possibly-, probably-, or definitely-related to study drug coded as CTCAE grades 3, 4, or 5.
Nested Study A3.1 Type of Short Intensive Therapy - MABS clearance from respiratory sample(s) with tolerance.
Time frame: Screening (Day 0) to the End of Short Intensive Therapy (Week 6).
Microbiological clearance of MABS from respiratory samples collected at 4 weeks with good tolerability assessed at the end of short intensive therapy between Arm D and the standard of care arms 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. Treatment tolerance is defined as no Treatment emergent adverse events and/or Treatment emergent adverse events that are "possibly-", "probably-", or "definitely-" related to study drug and coded as grade 1 or 2 based on the CTCAEv5.0.
Nested Study A3.2 - Duration of intensive therapy for patients completing short intensive treatment with ongoing positive MABS cultures collected at 4 weeks and randomised to either a further 6 weeks intensive therapy or immediate consolidation.
Time frame: Screening (Day 0) to EITHER the End of Prolonged Intensive Therapy (for those allocated to Prolonged Intensive) OR Week 12 Visit (for those allocated to immediate consolidation therapy).
To compare the microbiological clearance from samples collected at 10 weeks with good tolerability between those who are allocated to prolonged intensive therapy and those allocated to immediate consolidation following short intensive therapy. MABS clearance, assessed at the end of prolonged intensive therapy (for those allocated to prolonged intensive) or at 12 weeks (for those allocated to immediate consolidation) will be defined as negative MABS cultures from all 3 sputum samples or from one BAL sample collected at 10 weeks. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
16 secondary outcomes
Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway.
Time frame: Screening (Day 0); at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Incidence of Treatment emergent adverse events
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Safety of treatments based on changes in microbiological resistance.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in Forced Expiratory Volume in 1 second (FEV1) z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Phenotype of the structural abnormalities of chest Computer Tomography (CT) and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment.
Time frame: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Cystic Fibrosis Questionnaire - Respiratory domain (CFQ-R)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the EuroQol 5-Dimension (EQ-5D)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the St George's Respiratory Questionnaire (SGRQ)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Short Form (SF-36)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Pediatric Quality of Life Inventory (PedsQL)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Change in HRQoL (measured using the Child Health Utility 9 Dimensions (CHU-9D)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Cost effectiveness of the treatment combinations (measured using the Costs Questionnaire across intensive and consolidation phases of the trial.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Cost effectiveness of the treatment combinations (measured using Linked Administrative Healthcare Utilisation Data (for applicable jurisdictions)) across intensive and consolidation phases of the trial.
Time frame: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Causes for early withdrawal from MABS-PD treatment due to reasons other than poor tolerance as defined in the primary objectives.
Time frame: At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours), Ceftriaxone for Injection and Amoxicillin in people with Mycobacterium Abscessus Pulmonary Disease and Mycobacterium Abscessus Infection, run by The University of Queensland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Claire Wainwright Chief Investigator, MD (+61730697322, claire.wainwright@health.qld.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome of the Intervention Program is microbiological clearance of Mycobacterium abscessus (MABS) with good tolerance of the interventions. (time frame: Screening (Day 0) to End of treatment plus four weeks off-treatment (Final Outcome Visit (Week 56 for those allocated to Immediate Consolidation or Week 62 for those allocated to Prolonged Intensive).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026.