300 Participants Needed

Optimal Drug Regimen for Lung Disease

(FORMaT Trial)

Recruiting at 67 trial locations
RS
CW
KB
Overseen ByKara Brady, MPharm
Age: Any Age
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: The University of Queensland
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This trial tests different medicine combinations to find the best way to treat a tough lung infection in children and adults. The goal is to find the safest and most effective treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are receiving active treatment for MABS, you may not be eligible, except if you are taking azithromycin for cystic fibrosis and bronchiectasis.

Is the treatment generally safe for humans?

The treatment regimens, including drugs like amikacin, azithromycin, clarithromycin, and rifabutin, have been studied for safety. Amikacin was well tolerated in a study for pneumonia, but some patients experienced kidney-related side effects. Rifabutin, when used in high doses, caused side effects like reduced white blood cell counts and gastrointestinal issues, requiring dose adjustments in many patients.12345

What makes the drug regimen for lung disease unique?

This drug regimen for lung disease is unique because it combines multiple antibiotics and other medications, such as Amikacin, Azithromycin, and Linezolid, which are not typically used together in standard treatments for lung conditions. This combination may offer a novel approach by targeting the disease through different mechanisms, potentially improving effectiveness and addressing cases where standard treatments are not suitable.678910

What data supports the effectiveness of the drug regimen for lung disease?

The research indicates that amikacin, one of the drugs in the regimen, is used effectively in treating multidrug-resistant tuberculosis when combined with other drugs. Additionally, imipenem, another component, has shown effectiveness in treating resistant tuberculosis strains when used with clavulanate.1112131415

Eligibility Criteria

This trial is for people with a lung condition caused by Mycobacterium abscessus, who meet specific clinical, radiological, and microbiological criteria. It's open to those with mixed infections if needed for treatment. Participants must be able to follow the trial plan and visit schedule. Those treated for MABS in the last year (except certain cases), pregnant or breastfeeding individuals, or anyone allergic to the drugs tested cannot join.

Inclusion Criteria

I have been diagnosed with M. abscessus lung disease based on clinical, radiological, and microbiological criteria.
I have a mixed NTM infection and may need ethambutol as decided by my doctor.
You have at least one positive culture for bacteria in your respiratory system.
See 1 more

Exclusion Criteria

I haven't taken MABS treatment in the last year, except azithromycin for my cystic fibrosis.
You are allergic to the treatment options available for this study.
Pregnancy or planning to continue breastfeeding
See 1 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intensive Therapy

Participants receive intensive drug therapy including IV and inhaled antibiotics to clear MABS infection

6-12 weeks
Weekly visits for drug administration and monitoring

Consolidation Therapy

Participants receive oral and/or inhaled antibiotics to maintain MABS clearance

52-58 weeks
Monthly visits for monitoring and drug adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months
Quarterly visits for health assessments

Treatment Details

Interventions

  • Amikacin
  • Azithromycin
  • Cefoxitin
  • Clarithromycin
  • Clofazimine
  • Co-trimoxazole
  • Doxycycline
  • Ethambutol
  • Imipenem
  • Linezolid
  • Moxifloxacin
  • Rifabutin
  • Tigecycline
Trial Overview The FORMaT trial is testing a combination of antibiotics including Cefoxitin, Linezolid, Bedaquiline and others against MABS pulmonary disease. The goal is to find the best treatment regimen that maximizes health outcomes while minimizing toxicity and burden on patients.
Participant Groups
5Treatment groups
Experimental Treatment
Active Control
Group I: Intensive Therapy CExperimental Treatment7 Interventions
Following Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin.
Group II: Intensive Therapy BExperimental Treatment8 Interventions
Following Randomisation 1, Participants will receive inhaled amikacin (IA), IV tigecycline, IV cefoxitin/imipenem + oral azithromycin/oral clarithromycin AND clofazimine.
Group III: Consolidation BExperimental Treatment11 Interventions
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.
Group IV: Consolidation AActive Control10 Interventions
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.
Group V: Intensive Therapy AActive Control8 Interventions
Following Randomisation 1, Participants will receive intensive drug therapy in the form of IV amikacin, IV tigecycline, IV cefoxitin/imipenem + oral azithromycin AND clofazimine.

Amikacin is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Amikin for:
  • Serious infections caused by susceptible strains of gram-negative bacteria, including Pseudomonas species, Escherichia coli, Proteus species, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (formerly Mima-Herellea) species.
  • Initial empirical therapy, in hospital acquired infections, as part of a regimen, in serious infections where one or more of the following are the known or suspected pathogens: Pseudomonas aeruginosa, Serratia spp., and Providencia stuartii.
🇪🇺
Approved in European Union as Amikin for:
  • Serious infections caused by susceptible strains of gram-negative bacteria, including Pseudomonas aeruginosa and other Pseudomonas species, Escherichia coli, Klebsiella species, Enterobacter species, Serratia species, Citrobacter freundii, and Staphylococcus aureus (methicillin-resistant strains).

Find a Clinic Near You

Who Is Running the Clinical Trial?

The University of Queensland

Lead Sponsor

Trials
149
Recruited
71,700+

Monash University

Collaborator

Trials
204
Recruited
10,570,000+

Hôpital Cochin

Collaborator

Trials
30
Recruited
16,500+

Cystic Fibrosis Foundation

Collaborator

Trials
199
Recruited
37,800+

University of Melbourne

Collaborator

Trials
193
Recruited
1,287,000+

South Australian Health and Medical Research Institute

Collaborator

Trials
14
Recruited
6,800+

Australian Government Department of Health and Ageing

Collaborator

Trials
11
Recruited
21,000+

Griffith University

Collaborator

Trials
18
Recruited
22,900+

Children's Hospital Foundation

Collaborator

Trials
4
Recruited
450+

Newcastle University

Collaborator

Trials
172
Recruited
14,120,000+

Findings from Research

In a study of 833 patients with drug-sensitive tuberculosis, all five 6-month treatment regimens showed favorable bacteriological responses, with relapse rates of 2% or less for most regimens, except for one that had an 8% relapse rate due to the absence of pyrazinamide.
The study found low incidence of serious toxicity across all regimens, suggesting that these treatment options are safe, and the daily regimen may be particularly useful for self-administration in patients.
Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis.[2015]
In a study of 180 patients with multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB), meropenem/clavulanate showed significantly better treatment outcomes compared to imipenem/clavulanate, with higher sputum smear and culture conversion rates (94.8% vs 79.7% and 94.8% vs 71.9%, respectively).
The treatment success rate was also higher for meropenem/clavulanate at 77.5% compared to 59.7% for imipenem/clavulanate, indicating that meropenem/clavulanate may be a more effective option for these difficult-to-treat TB cases.
Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.Tiberi, S., Sotgiu, G., D'Ambrosio, L., et al.[2018]
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis can be effectively treated with a carefully selected combination of at least four antituberculosis drugs, tailored to the specific susceptibility of the Mycobacterium tuberculosis strain.
The treatment regimen involves a stepwise selection process based on drug efficacy, safety, and cost, utilizing groups of drugs including high-dose isoniazid, fluoroquinolones like levofloxacin, and injectable options such as capreomycin, ensuring a comprehensive approach to combat these resistant strains.
Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis.Caminero, JA., Sotgiu, G., Zumla, A., et al.[2022]

References

Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. [2015]
Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB. [2018]
Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. [2022]
4.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[Efficiency of a new standard chemotherapy regimen in the treatment of patients with recurrent pulmonary tuberculosis]. [2006]
Controlled trial of 4 three-times-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Second report: the results up to 24 months. Hong Kong Chest Service/British Medical Research Council. [2019]
Comparison of empiric aztreonam and aminoglycoside regimens in the treatment of serious gram-negative lower respiratory infections. [2022]
Safety considerations of current drug treatment strategies for nosocomial pneumonia. [2021]
Ceftazidime-Avibactam-Based Versus Tigecycline-Based Regimen for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae-Induced Pneumonia in Critically Ill Patients. [2021]
New antibiotics for Gram-negative pneumonia. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Early phase studies with paclitaxel/low-dose carboplatin in patients with solid tumors. [2015]
Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease. [2022]
First- and second-line therapy for advanced nonsmall cell lung cancer. [2018]
14.United Statespubmed.ncbi.nlm.nih.gov
A phase I study of carboplatin and paclitaxel in non-small cell lung cancer: a University of Colorado Cancer Center study. [2015]
[Stage IV NSCLC. Place of chemotherapy]. [2013]
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