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NCT Number: NCT02526004

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

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.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

16 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University College Cork

Cork, Ireland

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ceftazidime

Drug

Tobramycin

Drug

Primary outcomes

  1. The percentage change in recovery (post-exacerbation) FEV1 relative to the previous pre-exacerbation FEV1.

    Time frame: Time from enrollment to 14 days post initiation of IV antibiotics for elligible exacerbation.

Secondary outcomes

  1. The time to next pulmonary exacerbation

    Time frame: Time from pulmonary exacerbation day 0, to next pulmonary exacerbation up to study close month 21

  2. The improvement in symptom burden by day 7 as determined by Cystic Fibrosis Respiratory Symptom Diary (CFRSD)

    Time frame: Time from pulmonary exacerbation day 0 to day 7 of pulmonary exacerbation

    As determined by Cystic Fibrosis Respiratory Symptom Diary (CFRSD)

  3. The improvement in health related quality of life at day 28 post treatment and at 3 months as determined by the Cystic Fibrosis Questionnaire Revised (CFQR)

    Time frame: Time from pulmonary exacerbation day 0 to day 28 and month 3 post study treatment

    As determined by the Cystic Fibrosis Questionnaire Revised (CFQR)

  4. Total number of i.v. antibiotic days (home or in hospital) from time of randomisation in the trial

    Time frame: Time from enrollment in the study up to study close month 21

  5. Change in FEV1

    Time frame: Time from enrollment in the study up to study close month 21

  6. Total number of exacerbations post trial treatment

    Time frame: Time from pulmonary exacerbation day 0 to study close month 21

Sponsors and collaborators

Lead sponsor

University College Cork

Other

Collaborators

  • Assistance Publique - Hôpitaux de Paris
  • Clininfo S.A.
  • European Union
  • GABO:mi
  • KU Leuven
  • Papworth Hospital NHS Foundation Trust
  • Queen's University, Belfast
  • Teagasc
  • University Hospital Heidelberg
  • University of Dundee
  • University of Paris 5 - Rene Descartes
  • University of Washington

Registry information

Acronym: CFMATTERS

Important dates

Study start
2013
Primary completion
2017
Study completion
2018
First posted
Aug 18, 2015
Registry last updated
Apr 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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