Trial | NCT02526004  Report issue

Official Title

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

  • Phase

    N/A

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    223
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.
Study Started
Oct 01
2013
Primary Completion
Jun 30
2017
Study Completion
Jun 30
2018
Last Update
Jun 02
2022

Drug Ceftazidime

Drug Tobramycin

Standard Empiric Treatment Active Comparator

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

Microbiome Guided Treatment Experimental

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

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
No Results Posted