Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Valerie Waters, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00786513
First received: November 5, 2008
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. aeruginosa infection with an acute pulmonary exacerbation is a safe intervention that will result in improved microbiological and clinical outcomes and decrease markers of pulmonary inflammation.


Condition Intervention Phase
Cystic Fibrosis
Other: Conventional antimicrobial susceptibility testing
Other: Biofilm antimicrobial susceptibility testing
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Controlled Trial of the Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy in Chronic Pseudomonas Aeruginosa Infected Cystic Fibrosis Patients

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • The proportion of patients in the intervention arm versus the control arm who have ≥ 3 log drop in colony forming units (CFUs) of P. aeruginosa in sputum. [ Time Frame: Measured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change in pulmonary function tests, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal midexpiratory flow rate (FEF25-75) in the intervention arm versus the control arm [ Time Frame: Measured at day 0, day 7, and day 14 of antibiotic treatment and at the 1 month follow-up visit ] [ Designated as safety issue: No ]
  • The time to subsequent acute pulmonary exacerbation in the intervention arm versus the control arm [ Time Frame: 1 year following the completion of antibiotic therapy ] [ Designated as safety issue: No ]
  • The change in the cumulative score on a quality of life questionnaire in the intervention arm versus the control arm [ Time Frame: Measued at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit ] [ Designated as safety issue: No ]
  • The change in the measurement of markers of pulmonary inflammation (neutrophil counts, neutrophil elastase and IL-8 levels in sputum) in the intervention arm versus the control arm. [ Time Frame: Meaured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit ] [ Designated as safety issue: No ]

Enrollment: 134
Study Start Date: November 2008
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control Arm Other: Conventional antimicrobial susceptibility testing
Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on conventional planktonic antimicrobial susceptibility testing results.
Experimental: Intervention Arm Other: Biofilm antimicrobial susceptibility testing
Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on biofilm antimicrobial susceptibility testing results.

Detailed Description:

Cystic fibrosis (CF) is the most common fatal genetic condition in the Caucasian population and affects over 3,000 Canadians. Respiratory failure caused by chronic pulmonary infection is the primary cause of death in CF patients. The improved life expectancy of CF patients in the past several decades is due in part to the more aggressive use of antibiotics in the treatment of respiratory infections. However, there is currently no antimicrobial susceptibility assay that can predict which antibiotics will result in improved patient outcomes. Since Pseudomonas aeruginosa is known to grow as a resistant biofilm in the CF lung, antimicrobial susceptibility testing based on biofilm growth of P. aeruginosa may lead to different antibiotic choices that significantly decrease the pulmonary bacterial density of P. aeruginosa. A biofilm antimicrobial susceptibility assay thus has the ability to change the way antibiotics are chosen to treat CF patients and result in improved lung function and longer lives for all CF patients.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CF based on the following: sweat chloride > 60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF
  • Chronically infected with P. aeruginosa (>50% of respiratory specimens positive for P. aeruginosa in the 24 months prior to screening)
  • Able to produce sputum (expectorated or induced)
  • Able to reproducibility perform pulmonary function testing
  • Written informed consent provided

Exclusion Criteria:

  • Sputum culture negative for P. aeruginosa or with a density of less that 10^5 CFU/g at screening
  • Sputum culture positive for Burkholderia cepacia at screening
  • History of B. cepacia positive respiratory culture within 24 months prior to screening
  • Use of antibiotics other than those prescribed by the principal investigator
  • History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option
  • History of anaphylaxis or other life threatening complication to any antibiotic in the six groups that are a therapeutic option
  • Post lung transplantation or listed for lung transplantation
  • Pregnancy
  • A septic or clinically unstable patient
  • Presence of a condition or abnormality that in the opinion of an investigator would compromise the safety of the patient or the quality of the data
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786513

Locations
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada
BC Children's Hospital
Vancouver, British Columbia, Canada
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada
The Hospital for Sick Children
Toronto, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Valerie Waters, MD The Hospital for Sick Children
Principal Investigator: Yvonne Yau, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Valerie Waters, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00786513     History of Changes
Other Study ID Numbers: 1000011132
Study First Received: November 5, 2008
Last Updated: April 2, 2014
Health Authority: Canada: Ethics Review Committee

Keywords provided by The Hospital for Sick Children:
Cystic fibrosis
Pseudomonas aeruginosa
biofilm
antibiotic susceptibility testing
pediatrics

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Disease Susceptibility
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Disease Attributes
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on September 16, 2014