Early Intervention in Cystic Fibrosis Exacerbation (eICE)

• Change in FEV1 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  The primary outcome variable is FEV1 which will be obtained at quarterly study visits. The primary analysis will use a linear mixed effects model incorporating all FEV1 measurements to estimate the 52-week change in FEV1 and test for the differences between the two treatment groups (Early Intervention and Usual Care).
  
  

• Respiratory Symptom Scores (CFRSD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Change in CF respiratory symptoms as measured by the CFRSD will be analyzed using a linear mixed effects model incorporating baseline randomization factors FEV1 (<50%, 50-75%, and >75% predicted) and age (14-18 & 19+), treatment group, time (in weeks) and the interaction between treatment and time.
  
  
• Pulmonary Exacerbations [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Time to first acute protocol-defined pulmonary exacerbation and time from the start of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation will be analyzed using proportional hazards regression.
  
  
• Change in Health Related Quality of Life (QOL)Scores [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Change in health related quality of life as measured by the Cystic Fibrosis Questionnaire revised (CFQ-R)will be analyzed using a linear mixed effects model incorporating baseline randomization factors FEV1 (<50%, 50-75%, and >75% predicted) and age (14-18 & 19+), treatment group, time (in weeks) and the interaction between treatment and time.
  
  
• Treatment Burden [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Change in treatment burden as measured by the Cystic Fibrosis Questionnaire revised (CFQ-R)will be analyzed using a linear mixed effects model incorporating baseline randomization factors FEV1 (<50%, 50-75%, and >75% predicted) and age (14-18 & 19+), treatment group, time (in weeks) and the interaction between treatment and time.
  
  
• Change in prevalence of resistant species of bacteria [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Change in prevalence of resistant species of bacteria (Methicillin Resistant S. aureus, Multiply Resistant P. aeruginosa, B. cepacia, S. maltophilia, A xylosoxidans) in sputum between baseline and final visit (Visit 5 or early withdrawal) will be summarized by treatment group.
  
  
• Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  Adverse event rates will be coded by body system and MedDRA classification term. Adverse events will be tabulated by treatment group and will include the number of subjects for whom the event occurred, the rate of occurrence, and the severity and relationship to study participation or study procedures.
  
  

Individuals with CF develop chronic lung infections and suffer intermittent exacerbations, which require intensive treatment with antibiotics. The most common and useful objective measure of CF lung disease is spirometry. Chronic treatment of CF lung disease requires airway clearance, mucolytics and antibiotics. These treatments have been quite successful and there is evidence that early, aggressive treatment of lung disease results in better outcomes. Unfortunately, most exacerbations are not treated until they cause pronounced deterioration in symptoms, which prompts patients to seek medical attention. Self-monitoring of clinical status has improved outcomes in many other disorders such as asthma, diabetes mellitus, and lung transplantation. This is an important, randomized trial of home lung function and symptom monitoring in CF. Subjects will be assigned to one of two groups: 1) Home monitoring, in which spirometry and symptoms are recorded daily; or 2) Standard Care. The home monitoring data will be transmitted electronically twice weekly to the study center, where the results will be reviewed. If spirometry or symptoms have deteriorated substantially below baseline, treatment for a CF pulmonary exacerbation will be initiated. It is anticipated that use of home monitoring will translate into better clinical outcomes. We will test the hypothesis that if pulmonary exacerbations are identified and treated earlier than the current standard of care, the progression of lung disease will be slowed.