Saline Hypertonic in Preschoolers + CT
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this study is to assess whether inhalation of 7% hypertonic saline (HS) twice
      daily for 48 weeks reduces structural lung disease as assessed by computed tomography (CT) in
      comparison with inhalation of 0.9% isotonic saline (IS) in preschool children (ages 3 to 6)
      with cystic fibrosis.
    

Detailed description: 
      Several observational studies have shown that cystic fibrosis (CF) patients less than or
      equal to 6 years of age have clinically silent airway damage. There is growing interest in
      early initiation of therapies to prevent or delay the progression of this lung disease in CF.
      In SHIP-CT, the investigators will evaluate treatment effects of HS relative to IS on
      measures of structural lung disease obtained from chest CT using a novel scoring system
      sensitive to early lung changes, the Perth-Rotterdam Annotated Grid Morphometric Analysis
      method for CF (PRAGMA-CF), that quantifies the volume percentage of diseased airways (%Dis),
      bronchiectasis (%Bx), and trapped air (%TA). As a secondary evaluation of structural airway
      damage, the investigators will use an image analysis system to measure airway dimensions
      relative to adjacent arteries (AA-system). Longitudinal changes in CT measures will also be
      compared to changes in lung function measured by the lung clearance index (LCI) obtained by
      N2 Multiple Breath Washout (MBW) and to clinical outcomes.

      The primary hypothesis is that HS will reduce structural lung disease as assessed by the
      PRAGMA-CF computed tomography score relative to IS during the 48-week treatment period among
      preschool children with CF.

      SHIP-CT is a parallel study to SHIP001 (ClinicalTrials.gov Identifier NCT02378467). The
      primary hypothesis of SHIP001, which runs in North America, is that compared to IS, HS will
      improve the LCI, a measure of ventilation heterogeneity, during the 48-week treatment period
      among preschool children with CF. The SHIP-CT study (SHIP002) will use a nearly identical
      study design as the SHIP001 study, with similar eligibility criteria and treatment arms, to
      determine whether HS reduces structural lung disease as measured by chest computed tomography
      (CT), in addition to stabilizing or improving functional outcomes as measured by LCI.

      This is a multicenter, randomized, double-blind, controlled, parallel group trial assessing
      structural lung disease in children with CF ages 3 to 5 at enrollment. Participants will be
      randomized 1:1 to receive 7% hypertonic saline (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. Parents or the legal
      guardian will be contacted at Weeks 1, 4 and 8 to document changes in health status, adverse
      events, concomitant medications/treatments, and encourage study treatment compliance. Parents
      or the legal guardian will also be contacted approximately every 6 weeks between visit 3, 4,
      5, and 6 to address individual issues or concerns related to study treatment or study
      participation, and to document changes in health status, medications and treatments.

      Total duration of participant participation will be up to 53 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): Active Treatment Group 7% Hypertonic Saline; Control Group 0.9% Isotonic Saline
Intervention type(s): Drug; Drug
Intervention description(s): Drug: 7% Hypertonic Saline (HS) 4 mL of HS will be 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 compressor (PARI Vios® Pro in USA, PARI BOY SX in Australia and Europe).
Other Names:
Hyper-Sal™, inhaled saline; Drug: 0.9% Isotonic Saline (IS) 4 mL of IS will be administered via inhalation twice daily for 48 weeks The delivery system is the same as that for the test product.
Other Names: 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; Computed Tomography (CT)