Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy - Full Text View

Sponsored by:	The Hospital for Sick Children
Information provided by:	The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT00786513

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 II

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Antibiotics Cystic Fibrosis

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study
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

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 ]

Estimated Enrollment:	200
Study Start Date:	November 2008
Estimated Study Completion Date:	May 2012
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Control Arm: Active Comparator	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.
Intervention Arm: Experimental	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

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

Locations

Canada, Ontario
The Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada
Contact: Valerie Waters, MD (416)813-7654 ext 4541 valerie.waters@sickkids.ca
Principal Investigator: Valerie Waters, MD
Principal Investigator: Yvonne Yau, MD
Sub-Investigator: Felix Ratjen, MD
Sub-Investigator: Elizabeth Tullis, MD

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:	The Hospital for Sick Children ( Valerie Waters/Principal Investigator )
Study ID Numbers:	1000011132
Study First Received:	November 5, 2008
Last Updated:	November 5, 2008
ClinicalTrials.gov Identifier:	NCT00786513 History of Changes
Health Authority:	Canada: Ethics Review Committee

Keywords provided by The Hospital for Sick Children:

Cystic fibrosis
Pseudomonas aeruginosa
biofilm
antibiotic susceptibility testing
pediatrics

Study placed in the following topic categories:

Anti-Bacterial Agents
Digestive System Diseases
Genetic Diseases, Inborn
Respiratory Tract Diseases
Disease Susceptibility
Cystic Fibrosis

Fibrosis
Lung Diseases
Infant, Newborn, Diseases
Pancreatic Diseases
Genetic Predisposition to Disease

Additional relevant MeSH terms:

Anti-Infective Agents
Disease Attributes
Disease Susceptibility
Fibrosis
Pharmacologic Actions
Anti-Bacterial Agents
Digestive System Diseases
Pathologic Processes

Cystic Fibrosis
Respiratory Tract Diseases
Genetic Diseases, Inborn
Therapeutic Uses
Lung Diseases
Pancreatic Diseases
Infant, Newborn, Diseases
Genetic Predisposition to Disease

ClinicalTrials.gov processed this record on May 07, 2009