Comparison of Two Treatment Regimens to Reduce PA Infection in Children With Cystic Fibrosis
Condition: Cystic Fibrosis; Pulmonary Disease, Chronic Obstructive
MeSH terms: Cystic Fibrosis; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Fibrosis
Intervention: Tobramycin solution for inhalation (TOBI); Oral placebo; Oral ciprofloxacin
Intervention description: Tobramycin solution for inhalation, 300 mg, administered twice daily for 28 days administered only when quarterly respiratory cultures are found positive for Pa.; Oral placebo for six consecutive quarterly cycles. For the initial 14 days of the 28-day treatment period, the participants will receive placebo, twice daily.; Oral ciprofloxacin for six consecutive quarterly cycles. For the initial 14 days of the 28-day treatment period, the participants will receive oral ciprofloxacin, 15-20 mg/kg/dose, twice daily.
Intervention MeSH terms: Ciprofloxacin; Tobramycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 304.0
Sex: All
Minimum age: 1 Year
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Lung Diseases; Chronic Obstructive Pulmonary Disease

Summary:

      Cystic fibrosis (CF) is a chronic disease that significantly affects an individual's lung
      function. Antibiotic medications have been proven effective at reducing Pseudomonas
      aeruginosa (PA) infection, which is one of the main causes of death in individuals with CF.
      The purpose of this study is to compare the effectiveness of treatment based on quarterly
      culture results versus consistent quarterly antibiotic treatment at reducing PA infection in
      children with CF.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of CF, as determined by the 1997 CF Consensus Conference criteria: sweat
             chloride level greater than 60 milliequivalent/liter (mEq/L) by quantitative
             pilocarpine iontophoresis; or a genotype with two identifiable mutations consistent
             with CF; or an abnormal nasal transepithelial potential difference and one or more
             clinical features consistent with CF

          -  For participants greater than 15 months of age: documented new onset of positive
             oropharyngeal, sputum, or lower respiratory tract culture for PA within 6 months of
             study entry, defined as either: 1) first lifetime documented PA positive culture; or
             2) PA recovered after at least a 2-year history of PA negative respiratory cultures
             (at least one culture per year)

          -  For participants 12-15 months of age: at least one documented positive oropharyngeal,
             sputum, or lower respiratory tract culture for PA since birth or CF diagnosis

          -  Clinically stable with no evidence of any significant respiratory symptoms or chest
             radiograph findings at screening that would require administration of intravenous
             anti-pseudomonal antibiotics, oxygen supplementation, or hospitalization

        Exclusion Criteria:

          -  History of aminoglycoside hypersensitivity or adverse reaction to inhaled
             aminoglycoside

          -  History of hypersensitivity or adverse reaction to ciprofloxacin or other
             fluoroquinolone medications

          -  History of persistent, unresolved hearing loss documented by audiometric testing on at
             least two occasions and not associated with middle ear disease or an abnormal
             tympanogram

          -  Abnormal kidney function at study entry (defined as a serum creatinine level greater
             than 1.5 times the upper limit of normal for participant's age)

          -  Abnormal liver function test results at study entry (defined as alanine
             aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels greater than two
             times the upper limit of normal range)

          -  Use of any investigational drug within 30 days of study entry

          -  Use of loop diuretics, phenytoin, warfarin, theophylline, or other methylxanthines
             within 30 days of study entry

          -  Use of more than one course of intravenous anti-pseudomonal antibiotics (at least 10
             continuous days of medication use) or more than one course of inhaled anti-pseudomonal
             antibiotics (at least 28 continuous days of medication use) within 2 years of study
             entry; intravenous or inhaled anti-pseudomonal antibiotics must be stopped at least 30
             days prior to study entry

          -  Chronic macrolide use (more than 90 day duration) in the 3 months prior to study entry

          -  Presence of a condition or abnormality that would compromise the participant's safety
             or the quality of the study data, in the opinion of the investigator