Standard vs. Biofilm Susceptibility Testing in Cystic Fibrosis (CF)

Cystic Fibrosis Clinical Trial

Official title:

Standard vs. Biofilm Susceptibility Testing in CF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00153634
• Other study ID #: BURNS03A0
• Status: Completed
• Phase: N/A
• First received: September 8, 2005
• Last updated: March 12, 2008
• Start date: March 2004
• Est. completion date: November 2007

Study information

• Verified date: November 2007
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchitis
• Bronchitis, Chronic
• Chronic Bronchitis
• Cystic Fibrosis
• Disease Susceptibility
• Fibrosis

Intervention

Drug:
• IV amikacin
5-7.5 mg/kg every 8 hrs or previous dose; start at previous recent stable dose then monitor serum levels and adjust dose, if needed, per standard clinical practice at the site
• PO azithromycin
250 mg once daily
• IV ceftazidime
50 mg/kg every 8 hours, up to 2 grams every 8 hours
• PO ciprofloxacin
500 mg every 12 hours if weight <50 kg 750 mg every 12 hours if weight =50 kg
• IV meropenem
40 mg/kg every 8 hours, up to 2 grams every 8 hours
• IV piperacillin-tazobactam
100 mg/kg of piperacillin component every 6 hours, up to 3 grams every 6 hours; antibiotic combination formulated in a fixed ratio, thus dosing is described for first component only
• IV ticarcillin-clavulanate
100 mg/kg of ticarcillin component every 6 hours, up to 3 grams every 6 hours; antibiotic combination formulated in a fixed ratio, thus dosing is described for first component only
• IV tobramycin
2.5-3.3 mg/kg every 8 hrs or previous dose; start at previous recent stable dose then monitor serum levels and adjust dose, if needed, per standard clinical practice at the site

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Children's Hospital and Regional Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Washington University St. Louis	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Seattle Children's Hospital	Cystic Fibrosis Foundation Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. Epub 2005 Sep 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiological efficacy: Change in P. aeruginosa density		from enrollment (up to day -21) to end of treatment (day 12-14)
Secondary	Clinical efficacy: Pre- to post-treatment change in FEV1		from initiation (day 0) to end of treatment (day 12-14)
Secondary	Safety: Adverse events, including new onset of acute pulmonary exacerbation and/or the need to change antibiotic therapy during the treatment period		from enrollment (up to day -21) to end of treatment (day 12-14)
Secondary	Feasibility: Average costs and time per assay; rate of patient withdrawal because resistance patterns preclude randomization; self-reported technician satisfaction		during active enrollment (March 2004-November 2007)