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

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ClinicalTrials.gov Identifier: NCT02526004
Recruitment Status : Unknown
Verified August 2015 by Barry Plant, University College Cork.
Recruitment status was:  Recruiting
First Posted : August 18, 2015
Last Update Posted : August 18, 2015
Sponsor:
Collaborators:
Queen's University, Belfast
University of Paris 5 - Rene Descartes
University of Dundee
University of Washington
University Hospital Heidelberg
Teagasc
Clininfo S.A.
GABO:mi
Papworth Hospital
KU Leuven
Assistance Publique - Hôpitaux de Paris
European Union
Information provided by (Responsible Party):
Barry Plant, University College Cork

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Ceftazidime Drug: Tobramycin Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Cystic Fibrosis Microbiome-determined Antibiotic Therapy Trial in Exacerbations: Results Stratified
Study Start Date : January 2015
Estimated Primary Completion Date : September 2015
Estimated Study Completion Date : October 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Standard Empiric Treatment
Ceftazidime or Aztreonam (in case of Ceftazidime allergy) and Tobramycin
Drug: Ceftazidime
Drug: Tobramycin
Experimental: Microbiome Guided Treatment
Ceftazidime or Aztreonam (in case of Ceftazidime allergy) and Tobramycin and 3rd Antibiotic based on the Microbiome analysis
Drug: Ceftazidime
Drug: Tobramycin



Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  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 ]


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Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02526004


Contacts
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Contact: Barry J Plant, MD b.plant@ucc.ie
Contact: Joseph A Eustace, MD j.eustace@ucc.ie

Locations
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Ireland
University College Cork Recruiting
Cork, Ireland
Contact: Barry P Plant, MD         
Principal Investigator: Marcus Mall, MD         
Principal Investigator: Isabelle Fajac, MD         
Principal Investigator: Stuart Elborn, MD         
Principal Investigator: Charles Haworth, MD         
Principal Investigator: Christopher Goss, MD         
Principal Investigator: Lieven Dupont, MD         
Sponsors and Collaborators
University College Cork
Queen's University, Belfast
University of Paris 5 - Rene Descartes
University of Dundee
University of Washington
University Hospital Heidelberg
Teagasc
Clininfo S.A.
GABO:mi
Papworth Hospital
KU Leuven
Assistance Publique - Hôpitaux de Paris
European Union

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Responsible Party: Barry Plant, Barry Plant, CFMATTERS Coordinator, University College Cork
ClinicalTrials.gov Identifier: NCT02526004     History of Changes
Other Study ID Numbers: UCC-CFMATTERS
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: August 18, 2015
Last Verified: August 2015
Keywords provided by Barry Plant, University College Cork:
Cystic Fibrosis
Microbiome
Stratified Antibacterial therapy
Resistance
Pathogen Host Interaction
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Tobramycin
Ceftazidime