Clinical trial NCT00153634: Standard vs. Biofilm Susceptibility Testing in Cystic Fibrosis (CF)
Official title: Standard vs. Biofilm Susceptibility Testing in CF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Chronic Bronchitis
Keywords: Cystic fibrosis
Antibiotic susceptibility testing
Pseudomonas aeruginosa
Chronic bronchitis
Biofilms
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2005-09-12
Enrollment: 75
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a randomized multi-center clinical trial to compare the microbiological efficacy, clinical efficacy, and safety of using standard versus biofilm susceptibility testing of P. aeruginosa sputum isolates to guide antibiotic selection for treatment of airway infection in clinically stable patients with CF.

Detailed description: Patients were screened to determine eligibility and to obtain a sputum culture. Eligible patients were randomized to either the standard or biofilm study arm. Antibiotic selection was performed centrally according to a standard algorithm using the susceptibility test results of the assigned study arm. On Day 0, patients were started on a 14-day course of two antibiotics as selected per protocol. Antibiotics were administered intravenously (IV) and/or orally. A follow-up phone call or visit occurred on Day 7. An end of treatment visit was conducted after completion of antibiotic therapy. A total of 39 patients were randomized. Many screened patients were ineligible for randomization based on microbiology results.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of CF based on the following: sweat chloride \> 60 mEq/L (by quantitative pilocarpine iontophoresis), or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF.
* Age ≥ 14 years (changed from ≥ 18 years by protocol amendment).
* Able to expectorate sputum at screening.
* History of persistent positivity for P. aeruginosa on respiratory culture (at least three positive oropharyngeal (OP), sputum and/or bronchoscopy cultures in the 24 months prior to screening).
* Able to reproducibly perform pulmonary function testing.
* Clinically stable at screening, with no evidence of pulmonary exacerbation.
* Written informed consent provided.

Exclusion Criteria:

* Sputum culture negative for P. aeruginosa or density less than 10E5 CFU/gm at screening.
* Sputum culture positive for B. cepacia at screening.
* Presence of P. aeruginosa in sputum with off-scale resistance to all antibiotics by either method of susceptibility testing at screening. (changed from multiply-resistant P. aeruginosa by protocol amendment)
* History of B. cepacia positive respiratory culture within 24 months prior to screening.
* Hospitalization or treatment for a pulmonary exacerbation within 2 months prior to screening.
* Administration of parenteral anti-pseudomonal antibiotics within 2 months prior to screening.
* Treatment with oral or inhaled anti-pseudomonal antibiotics, or azithromycin or other macrolides within 14 days prior to screening.
* 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.
* History of abnormal renal function (serum creatinine \> 1.5 x upper limit of normal) within one year of enrollment.
* History of abnormal liver function tests (\> 2.5 x upper limit of normal) within one year of enrollment.
* Clinically documented hearing loss that precludes treatment with aminoglycosides.
* Post lung transplantation.
* Positive pregnancy test or female who is lactating or is not practicing an acceptable method of birth control.
* 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.
* Administration of any investigational agent within 30 days prior to screening.

Primary outcomes:
measure: Microbiological efficacy: Change in P. aeruginosa density
timeFrame: from enrollment (up to day -21) to end of treatment (day 12-14)
Secondary outcomes:
measure: Clinical efficacy: Pre- to post-treatment change in FEV1
timeFrame: from initiation (day 0) to end of treatment (day 12-14)
measure: Safety: Adverse events, including new onset of acute pulmonary exacerbation and/or the need to change antibiotic therapy during the treatment period
timeFrame: from enrollment (up to day -21) to end of treatment (day 12-14)
measure: Feasibility: Average costs and time per assay; rate of patient withdrawal because resistance patterns preclude randomization; self-reported technician satisfaction
timeFrame: during active enrollment (March 2004-November 2007)
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: St. Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Samuel M Moskowitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital and Regional Medical Center
name: Jane L Burns, MD
role: STUDY_CHAIR
References:
citation: Moskowitz SM, Foster JM, Emerson J, Burns JL. Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol. 2004 May;42(5):1915-22. doi: 10.1128/JCM.42.5.1915-1922.2004.
citation: Moskowitz SM, Foster JM, Emerson JC, Gibson RL, Burns JL. Use of Pseudomonas biofilm susceptibilities to assign simulated antibiotic regimens for cystic fibrosis airway infection. J Antimicrob Chemother. 2005 Nov;56(5):879-86. doi: 10.1093/jac/dki338. Epub 2005 Sep 27.