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Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Conventional antimicrobial susceptibility testing

Biofilm antimicrobial susceptibility testing

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic fibrosis, Pseudomonas aeruginosa, biofilm, antibiotic susceptibility testing, pediatrics

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

BC Children's Hospital
St. Paul's Hospital
Hamilton Health Sciences
St. Michael's Hospital
The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control Arm

Intervention Arm

Arm Description

Outcomes

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.

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

The time to subsequent acute pulmonary exacerbation in the intervention arm versus the control arm

The change in the cumulative score on a quality of life questionnaire in the intervention arm versus the control arm

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.

Full Information

NCT ID

NCT00786513

First Posted

November 5, 2008

Last Updated

April 2, 2014

Sponsor

The Hospital for Sick Children

1. Study Identification

Unique Protocol Identification Number

NCT00786513

Brief Title

Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

March 2014 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Hospital for Sick Children

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

Cystic fibrosis, Pseudomonas aeruginosa, biofilm, antibiotic susceptibility testing, pediatrics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

134 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control Arm

Arm Type

Active Comparator

Arm Title

Intervention Arm

Arm Type

Experimental

Intervention Type

Other

Intervention Name(s)

Conventional antimicrobial susceptibility testing

Intervention Description

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 Type

Other

Intervention Name(s)

Biofilm antimicrobial susceptibility testing

Intervention Description

Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on biofilm antimicrobial susceptibility testing results.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

Measured at day 0, day 7, and day 14 of antibiotic treatment and at the 1 month follow-up visit

Title

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

Title

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

Title

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

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Valerie Waters, MD

Organizational Affiliation

The Hospital for Sick Children

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yvonne Yau, MD

Organizational Affiliation

The Hospital for Sick Children

Official's Role

Principal Investigator

Facility Information:

Facility Name

BC Children's Hospital

City

Vancouver

State/Province

British Columbia

Country

Canada

Facility Name

St. Paul's Hospital

City

Vancouver

State/Province

British Columbia

Country

Canada

Facility Name

Hamilton Health Sciences

City

Hamilton

State/Province

Ontario

Country

Canada

Facility Name

St. Michael's Hospital

City

Toronto

State/Province

Ontario

Country

Canada

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

25453872

Citation

Yau YC, Ratjen F, Tullis E, Wilcox P, Freitag A, Chilvers M, Grasemann H, Zlosnik J, Speert D, Corey M, Stanojevic S, Matukas L, Leahy TR, Shih S, Waters V. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J Cyst Fibros. 2015 Mar;14(2):262-6. doi: 10.1016/j.jcf.2014.09.013. Epub 2014 Oct 30.

Results Reference

derived

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Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

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