This is a randomized multi-center clinical trial that will 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.

Condition	Intervention
Cystic Fibrosis Chronic Bronchitis	Drug: IV amikacin  Drug: PO azithromycin  Drug: IV ceftazidime  Drug: PO ciprofloxacin  Drug: IV meropenem  Drug: IV piperacillin-tazobactam  Drug: IV ticarcillin-clavulanate  Drug: IV tobramycin

Further Study Details: 

Primary Outcomes: Microbiological efficacy: Change in P. aeruginosa density from baseline (up to day -21) to end of treatment (day 14)
Secondary Outcomes: Clinical efficacy: Pre- to post-treatment change in FEV1; Safety: Adverse events, including new onset of acute pulmonary exacerbation and/or the need to change antibiotic therapy during the treatment period; Feasibility: Average costs and time per assay; rate of patient withdrawal because resistance patterns preclude randomization; self-reported technician satisfaction; Surrogate Marker of Biofilm Formation: N-acyl homoserine lactones in CF sputum
Expected Total Enrollment:  50

Patients will be screened to determine eligibility and to obtain a sputum culture. Eligible patients will be randomized to either the standard or biofilm study arm. Antibiotic selection will be performed centrally according to a standard algorithm using the susceptibility test results of the assigned study arm. On Day 0, patients will be started on a 14-day course of two antibiotics as selected per protocol. Antibiotics will be administered intravenously (IV) and/or orally. A follow-up phone call or visit will occur on Day 7. An end of treatment visit will be conducted after completion of antibiotic therapy. A total of 50 patients (25 per arm) will be randomized with the expectation of having 40 patients with primary endpoint data at the end of treatment visit. It is anticipated that some screened patients will be ineligible for randomization based on microbiology results, therefore the number of patients screened at Visit 1 will depend on the number who are eligible for treatment.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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 ≥ 18 years.
• 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 that is multiply resistant to antibiotics by either method of susceptibility testing at screening.
• 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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00153634

Sharon McNamara, MN      206-987-1313    sharon.mcnamara@seattlechildrens.org

Iowa
      University of Iowa, Iowa City,  Iowa,  52242,  United States; Recruiting
Missouri
      Washington University St. Louis, St. Louis,  Missouri,  63110,  United States; Not yet recruiting
Ohio
      Ohio State University, Columbus,  Ohio,  43205,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Medical Center, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
Washington
      Children''''s Hospital and Regional Medical Center, Seattle,  Washington,  98105-0371,  United States; Recruiting
      University of Washington Medical Center, Seattle,  Washington,  98195,  United States; Recruiting

Study chairs or principal investigators

Samuel M Moskowitz, MD,  Principal Investigator,  Children''''s Hospital and Regional Medical Center, Seattle   
Jane L Burns, MD,  Study Chair,  Children''''s Hospital and Regional Medical Center   

Study ID Numbers:  BURNS03A0
Last Updated:  September 9, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00153634
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-13