Cystic Fibrosis Microbiome-determined Antibiotic Therapy Trial in Exacerbations: Results Stratified

NCT ID: NCT02526004

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 223 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-01
• Study Completion Date: 2018-06-30

Brief Summary

Antimicrobial resistance is a significant challenge facing global healthcare. The unnecessary use of antibiotics is a key driver in the development of antibiotic resistance. Cystic Fibrosis (CF) represents a unique disease model to study bacterial resistance and to explore therapeutic strategies for same, as chronic lung infection overlaps with acute lung exacerbation's caused by a multitude of organisms. With time, chronic polymicrobial infection develops, with the most dominant infecting organism being Pseudomonas aeruginosa. In acute CF infections, empiric intravenous antibiotics are usually given for two weeks. Recurrent infections and treatments result in increasing antimicrobial resistance, and alterations in pathogen host interactions in the lung and gut flora. Next-generation DNA sequencing technology now offers DNA-based personalised diagnostics and treatment strategies. Enhancing our knowledge of the microbiome allows the use of stratified targeted antibacterial therapy that can be compared with standard empirical antibacterial therapy currently used. Cystic Fibrosis Microbiome-determined Antimicrobial Therapy Trial in Exacerbations: Results Stratified (CFMATTERS) will provide a randomized multi-centre controlled trial of microbiome-derived antimicrobial treatments versus current empirical therapy.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Study Groups

Standard Empiric Treatment

Ceftazidime or Aztreonam (in case of Ceftazidime allergy) and Tobramycin

Group Type: ACTIVE_COMPARATOR

Ceftazidime

Intervention Type: DRUG

Tobramycin

Intervention Type: DRUG

Microbiome Guided Treatment

Ceftazidime or Aztreonam (in case of Ceftazidime allergy) and Tobramycin and 3rd Antibiotic based on the Microbiome analysis

Group Type: EXPERIMENTAL

Ceftazidime

Intervention Type: DRUG

Tobramycin

Intervention Type: DRUG

Interventions

Ceftazidime

Intervention Type: DRUG

Tobramycin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written and informed consent, and assent where required.
• Age 16 years or older at enrolment
• Diagnosis of CF by standard sweat test and/or genetic analysis
• Persistent pulmonary Pseudomonas aeruginosa colonization confirmed on at least 2 occasions in the preceding 12 months
• Screening FEV1 predicted of >25%
• Able to perform spirometry reproducibly prior to enrolment
• Able to expectorate and provide a sputum sample at least once daily
• ≥1 non-elective course of intravenous antibiotics in the preceding year
• Able to understand and comply with protocol requirements, restrictions and instructions and likely to complete the study as planned, as judged by the investigator

Exclusion Criteria

• Life expectancy less than 6 months
• They are a solid organ transplant recipient
• Have a requirement for immunosuppression ≥10mg corticosteroids per day
• Previous positive culture of non-tuberculosis mycobacteria species M.avium, M.abscessus or M.intracellulare within the last 12 months or undergoing active therapy
• Positive culture of any Burkholderia cepacia species within the last 12 months or undergoing active therapy
• Allergic bronchopulmonary aspergillosis on treatment
• Known allergies to more than 3 different classes of antibiotics, and intolerance or allergy to tobramycin.
• Liver portal hypertension, determined by identification of oesophageal varices
• Advanced kidney disease requiring a dose reduction of ceftazidime or contraindicating aminoglycosides
• History of any illness that in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject
• If patient undergoes a pulmonary exacerbation before the Microbiome analysis is reviewed by the Consensus Treatment Panel and i.v. antibiotics are administered. In this case, a repeat sputum will be sent for analysis 4 weeks after end of antibiotic treatment.
• Pregnant or breast-feeding at time of eligible pulmonary exacerbation

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Queen's University, Belfast

OTHER

Sponsor Role: collaborator

University of Paris 5 - Rene Descartes

OTHER

Sponsor Role: collaborator

University of Dundee

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: collaborator

University Hospital Heidelberg

OTHER

Sponsor Role: collaborator

Teagasc

INDUSTRY

Sponsor Role: collaborator

Clininfo S.A.

INDUSTRY

Sponsor Role: collaborator

GABO:mi

INDUSTRY

Sponsor Role: collaborator

Papworth Hospital NHS Foundation Trust

OTHER_GOV

Sponsor Role: collaborator

KU Leuven

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

European Union

OTHER

Sponsor Role: collaborator

University College Cork

OTHER

Sponsor Role: lead

Responsible Party

Barry Plant

Barry Plant, CFMATTERS Coordinator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University College Cork

Cork, Cork, Ireland

Countries

Ireland

Other Identifiers

UCC-CFMATTERS

Identifier Type: -

Identifier Source: org_study_id