Clinical trial NCT02950883: Saline Hypertonic in Preschoolers + CT
Official title: Saline Hypertonic in Preschoolers With Cystic Fibrosis and Lung Structure as Measured by Computed Tomography (CT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Cystic Fibrosis
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)
Lead sponsor: University of Washington, the Collaborative Health Studies Coordinating Center
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2016-11-01
Enrollment: 116
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of CF as evidenced by one or more clinical features consistent with the CF phenotype or positive CF newborn screen AND one or more of the following criteria:

   1. A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis (QPIT)
   2. A documented genotype with two disease-causing mutations in the CFTR gene
2. Informed consent by parent or legal guardian
3. Age ≥ 36 months and ≤72 months at screening visit
4. Ability to comply with medication use, study visits and study procedures as judged by the site investigator
5. Ability to cooperate with chest CT at the enrollment visit as determined by the lung function technician

Exclusion Criteria:

1. Chest CT within 8 months prior to the Screening visit
2. Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding screening or enrollment visit
3. Acute wheezing at screening or enrollment visit
4. Oxygen saturation \< 95% (\<90% in centers located above 4000 feet elevation) at screening or enrollment visit
5. Other major organ dysfunction, excluding pancreatic dysfunction
6. Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator
7. Investigational drug use within 30 days prior to screening or enrollment visit
8. Treatment with inhaled HS at any concentration within 30 days prior to screening or enrollment visit
9. Initiation (i.e. new prescription) of any inhaled hydrating agent such as mannitol or mucolytic agents such as dornase alpha within 30 days prior to the screening or enrollment visit
10. Chronic lung disease not related to CF
11. Inability to tolerate first dose of study treatment at the enrollment visit

Primary outcomes:
measure: Chest CT
timeFrame: 48 weeks
Secondary outcomes:
measure: PRAGMA-CF Sub-scores
timeFrame: 48 weeks
measure: Lung Clearance Index (LCI)
timeFrame: 48 weeks
measure: Cross-sectional and longitudinal relationships
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Adelaide
country: Australia
facility: Royal Women's and Children Hospital
city: Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
city: Melbourne
country: Australia
facility: Royal Children's Hospital
city: Newcastle
country: Australia
facility: John Hunter Children's Hospital
city: Sydney
country: Australia
facility: Children's Hospital at Westmead
city: Sydney
country: Australia
facility: Sydney Children's Hospital at Randwick
city: West Perth
country: Australia
facility: Perth Children's Hospital
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Children's Hospital
city: Leuven
country: Belgium
facility: UZ Leuven - Gasthuisberg Ziekenhuis
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Hospital for Sick Kids
state: Ontario
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital Rigshospitalet
city: Lyon
country: France
facility: Hospice Civils de Lyon
city: Paris
country: France
facility: Hospital Robert Debre
city: Roma
country: Italy
facility: Bambini Gesu Children's Hospital
city: Verona
country: Italy
facility: Ospedale Civile Maggiore
city: Rotterdam
country: Netherlands
facility: Sophia Children's Hospital at Erasmus Medical Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
affiliation: Erasmus Medical Centre, Rotterdam
name: Harm Tiddens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Telethon Kids Institute, Perth
name: Stephen Stick, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital, Seattle
name: Margaret Rosenfeld, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University, Indianapolis
name: Stephanie Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Felix Ratjen, MD, PhD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosenow T, Oudraad MC, Murray CP, Turkovic L, Kuo W, de Bruijne M, Ranganathan SC, Tiddens HA, Stick SM; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis. Am J Respir Crit Care Med. 2015 May 15;191(10):1158-65. doi: 10.1164/rccm.201501-0061OC.
citation: Ramsey KA, Rosenow T, Turkovic L, Skoric B, Banton G, Adams AM, Simpson SJ, Murray C, Ranganathan SC, Stick SM, Hall GL; AREST CF. Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis. Am J Respir Crit Care Med. 2016 Jan 1;193(1):60-7. doi: 10.1164/rccm.201507-1409OC.
citation: Tiddens HAWM, Chen Y, Andrinopoulou ER, Davis SD, Rosenfeld M, Ratjen F, Kronmal RA, Hinckley Stukovsky KD, Dasiewicz A, Stick SM; SHIP-CT Study Group. The effect of inhaled hypertonic saline on lung structure in children aged 3-6 years with cystic fibrosis (SHIP-CT): a multicentre, randomised, double-blind, controlled trial. Lancet Respir Med. 2022 Jul;10(7):669-678. doi: 10.1016/S2213-2600(21)00546-4. Epub 2022 Mar 11.