- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02526004
Cystic Fibrosis Microbiome-determined Antibiotic Therapy Trial in Exacerbations: Results Stratified (CFMATTERS)
June 1, 2022 updated by: Barry Plant, University College Cork
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 Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
223
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Cork, Ireland
- University College Cork
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 80 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Standard Empiric Treatment
Ceftazidime or Aztreonam (in case of Ceftazidime allergy) and Tobramycin
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Experimental: Microbiome Guided Treatment
Ceftazidime or Aztreonam (in case of Ceftazidime allergy) and Tobramycin and 3rd Antibiotic based on the Microbiome analysis
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The percentage change in recovery (post-exacerbation) FEV1 relative to the previous pre-exacerbation FEV1.
Time Frame: Time from enrollment into the study up to study close month 21
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Time from enrollment into the study up to study close month 21
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The time to next pulmonary exacerbation
Time Frame: Time from pulmonary exacerbation day 0, to next pulmonary exacerbation up to study close month 21
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Time from pulmonary exacerbation day 0, to next pulmonary exacerbation up to study close month 21
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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
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As determined by Cystic Fibrosis Respiratory Symptom Diary (CFRSD)
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Time from pulmonary exacerbation day 0 to day 7 of pulmonary exacerbation
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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
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As determined by the Cystic Fibrosis Questionnaire Revised (CFQR)
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Time from pulmonary exacerbation day 0 to day 28 and month 3 post study treatment
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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
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Time from enrollment in the study up to study close month 21
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Change in FEV1
Time Frame: Time from enrollment in the study up to study close month 21
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Time from enrollment in the study up to study close month 21
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Total number of exacerbations post trial treatment
Time Frame: Time from pulmonary exacerbation day 0 to study close month 21
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Time from pulmonary exacerbation day 0 to study close month 21
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2013
Primary Completion (Actual)
June 30, 2017
Study Completion (Actual)
June 30, 2018
Study Registration Dates
First Submitted
August 10, 2015
First Submitted That Met QC Criteria
August 17, 2015
First Posted (Estimate)
August 18, 2015
Study Record Updates
Last Update Posted (Actual)
June 2, 2022
Last Update Submitted That Met QC Criteria
June 1, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UCC-CFMATTERS
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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