Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy

NCT00786513 | Completed Phase 2

• 1 other identifier: 1000011132
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 5

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.

Conditions

Cystic Fibrosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• 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

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

  1 year following the completion of antibiotic therapy

• 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

• 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

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Other: Conventional antimicrobial susceptibility testing

Intervention Arm

EXPERIMENTAL

Other: Biofilm antimicrobial susceptibility testing

Interventions

Conventional antimicrobial susceptibility testing OTHER

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

Control Arm

Biofilm antimicrobial susceptibility testing OTHER

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

Intervention Arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (5)

BC Children's Hospital

Vancouver, British Columbia, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 25453872 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Valerie Waters, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Yvonne Yau, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: November 5, 2008
• First Posted: November 6, 2008
• Study Start: November 1, 2008
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 4, 2014

Record last verified: 2014-04

Locations

CA (5)