Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00786513
• Other study ID #: 1000011132
• Status: Completed
• Phase: Phase 2
• First received: November 5, 2008
• Last updated: April 2, 2014
• Start date: November 2008
• Est. completion date: March 2014

Study information

• Verified date: April 2014
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Disease Susceptibility
• Fibrosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	BC Children's Hospital	Vancouver	British Columbia
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Measured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit	No
Secondary	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		Measured at day 0, day 7, and day 14 of antibiotic treatment and at the 1 month follow-up visit	No
Secondary	The time to subsequent acute pulmonary exacerbation in the intervention arm versus the control arm		1 year following the completion of antibiotic therapy	No
Secondary	The change in the cumulative score on a quality of life questionnaire in the intervention arm versus the control arm		Measued at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit	No
Secondary	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.		Meaured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit	No