title: Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'.
abstract: BACKGROUND
  The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood.
  
  
  OBJECTIVE
  The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture.
  
  
  METHODS
  The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1-12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15-20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1787 were enrolled in the cohort study.
  
  
  CONCLUSIONS
  These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the airways of young children with CF.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA. treggmm@u.washington.edu
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Treggiari
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.forename: George
authors.initials: G
authors.lastname: Retsch-Bogart
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gibson
authors.forename: Judy
authors.initials: J
authors.lastname: Williams
authors.forename: Julia
authors.initials: J
authors.lastname: Emerson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012307:Risk Factors; D014031:Tobramycin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D014031:Tobramycin