Saline Hypertonic in Preschoolers
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional

Summary: 
      The purpose of this study is to assess whether inhalation of 7% hypertonic saline (HS) twice
      daily for 48 weeks improves the lung clearance index by multiple breath nitrogen washout in
      comparison with inhalation of 0.9% isotonic saline (IS) in preschool children (ages 3 to 5)
      with cystic fibrosis.
    

Detailed description: 
      A growing body of evidence supports the importance of intervention in cystic fibrosis (CF)
      lung disease during early childhood, in order to potentially delay or prevent irreversible
      lung damage. Yet, aside from antimicrobial therapies, the CF community has no clinical trial
      evidence base with which to guide chronic pulmonary therapies in preschool children.
      Hypertonic saline (HS) is the most attractive chronic maintenance therapy to investigate in
      preschool 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.

      Based on several studies, HS appears to be safe in children less than 6 years of age, but its
      effectiveness has been difficult to measure. In a previous study (ISIS), children less than 6
      years old receiving HS had the same number of lung infections as children receiving a control
      treatment. However, the investigators think that children this young need a more sensitive
      test, such as lung function testing, to see if HS works in preventing lung damage. Multiple
      Breath Washout (MBW) is a relatively easy lung function test to perform with preschool
      children. It calculates a measurement called the Lung Clearance Index (LCI), a sensitive
      measure of airway inhomogeneity. In a sub-study of the ISIS study in 25 children, LCI
      improved in children that inhaled HS twice daily for 48 weeks.

      This is a multicenter, randomized, double-blind, controlled, parallel group trial assessing
      LCI in children with CF ages 3 to 5 at enrollment. Participants will be randomized 1:1 to
      receive 7% HS (treatment arm) vs. 0.9 % isotonic saline (control arm) administered twice
      daily via jet nebulizer for 48 weeks. Study visits will occur at Screening, Enrollment, and
      at Weeks 12, 24, 36 and 48. Contact with a parent or legal guardian to assess adherence and
      interim medical history will occur at 1, 4 and 8 weeks after enrollment and then quarterly
      between subsequent study visits. Except for the screening visit, study visits will occur on a
      quarterly basis.

      Total duration of participation will be up to 52 weeks. As enrollment will occur over
      approximately 18 months, total duration of the study is expected to be up to 30 months (18
      months enrollment plus 12 months for the last participants to complete study participation).
    

Intervention name(s): 7% Hypertonic Saline (HS); 0.9% Isotonic Saline (IS)
Intervention type(s): Drug; Drug
Intervention description(s): Administered via inhalation twice daily for 48 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Vios® compressor.; Administered via inhalation twice daily for 48 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Vios® compressor.
Other intervention name(s): Hyper-Sal™, inhaled saline; Normal saline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cystic Fibrosis; Hypertonic Saline; Inhaled Saline; Digestive System Diseases; Genetic Diseases, Inborn; Lung Diseases; Pancreatic Diseases; Pathologic Processes; Respiratory Tract Diseases