Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS)

• The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS [ Time Frame: during the 48 week treatment period ] [ Designated as safety issue: Yes ]
  

• Symptoms by parent home questionnaire administered weekly [ Time Frame: during the 48 week treatment period ] [ Designated as safety issue: Yes ]
  
• Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: No ]
  
• Standardized cough score assessed at study visits [ Time Frame: during the 48 week treatment period ] [ Designated as safety issue: No ]
  
• Change in weight, height, resting respiratory rate, and room air oxygen saturation [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: Yes ]
  
• Among participants from whom Pseudomonas aeruginosa (Pa) and other CF pathogens were not isolated from respiratory cultures prior to enrollment, the proportion from whom these organisms are isolated from clinically collected respiratory cultures [ Time Frame: measured at baseline and at 48 weeks ] [ Designated as safety issue: Yes ]
  
• Pulmonary function indices measured at baseline and 48 weeks in infants 4 to 15 months of age at enrollment participating in infant pulmonary function testing (N = 100, selected sites) [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: No ]
  

A growing body of evidence supports the importance of intervention in Cystic Fibrosis (CF) lung disease during infancy and early childhood, in order to potentially delay or prevent irreversible lung disease. Yet, aside from antimicrobial therapies, the CF community has no clinical trial evidence base with which to guide pulmonary therapies in children <6 years of age. Hypertonic Saline (HS) is the most attractive chronic maintenance therapy to investigate in these young children because it addresses defective mucociliary clearance, an early step in the cascade of events leading to CF lung disease that is expected to be abnormal prior to the onset of airway infection and inflammation.

This study is a randomized, parallel group, controlled trial to assess the efficacy and safety of 7% HS inhaled twice daily for 48 weeks among young children with CF 4 to < 60 months of age at enrollment. The primary hypothesis is that, compared to isotonic saline (IS), HS will decrease the number of protocol-defined pulmonary exacerbations during the 48 week treatment period. The results of the proposed trial may for the first time provide evidence for early initiation of HS, which, by improving mucociliary clearance, may delay or hinder the cycle of infection and inflammation responsible for progressive airway damage in CF lung disease.