SHIP-CT: Saline Hypertonic in Preschoolers + CT

• Sponsor: University of Washington, the Collaborative Health Studies Coordinating Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02950883
• Collaborator: Cystic Fibrosis Foundation (Other)
• Enrollment: 116
• Locations: 25
• Arms: 2
• Actual Duration (Months): 75.1
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Active Treatment Group 7% Hypertonic Saline; Drug: Control Group 0.9% Isotonic Saline	Phase 2/Phase 3

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Saline Hypertonic in Preschoolers With Cystic Fibrosis and Lung Structure as Measured by Computed Tomography (CT)
• Actual Study Start Date: Mar 24, 2015
• Actual Primary Completion Date: Dec 15, 2020
• Actual Study Completion Date: Jun 25, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Treatment Group 7% Hypertonic Saline administered via inhalation twice daily for 48 weeks	Drug: Active Treatment Group 7% Hypertonic Saline; 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
Active Comparator: Control Group 0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks	Drug: Control Group 0.9% Isotonic 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

Outcome Measures

Primary Outcome Measures

1. Chest CT [48 weeks]

   The difference in PRAGMA-CF %Dis between HS and IS study arm at end of study (48 weeks), adjusted for baseline, measured from standardized chest CT.

Secondary Outcome Measures

1. PRAGMA-CF Sub-scores [48 weeks]

   i) The difference in PRAGMA-CF sub-scores, %Bx (the volume proportion of the lung with bronchiectasis) and %TA (the volume proportion of the lung with trapped air), between the baseline CT and the 48 week CT. ii) The absolute number of airways, airway dimensions and AA ratios from TLC CTs, acquired at the 48-week visit.

2. Lung Clearance Index (LCI) [48 weeks]

   The difference in LCI, measured by N2 MBW, from baseline to 48 weeks

3. Cross-sectional and longitudinal relationships [48 weeks]

   Cross-sectional and longitudinal relationships between primary and secondary PRAGMA-CF outcomes (%Dis, %Bx and %TA) and MBW outcomes (LCI), airway dimensions and PRAGMA-CF and MBW outcomes, as well as CFQ-R scores and PRAGMA-CF and MBW

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 5 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

2. A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis (QPIT)

3. A documented genotype with two disease-causing mutations in the CFTR gene

4. Informed consent by parent or legal guardian

5. Age ≥ 36 months and ≤72 months at screening visit

6. Ability to comply with medication use, study visits and study procedures as judged by the site investigator

7. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Colorado	Aurora	Colorado	United States	80045
2	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
5	Oregon Health Sciences University	Portland	Oregon	United States	97239
6	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
7	Seattle Children's Hospital	Seattle	Washington	United States	98105
8	Royal Women's and Children Hospital	Adelaide		Australia
9	Lady Cilento Children's Hospital	Brisbane		Australia
10	Royal Children's Hospital	Melbourne		Australia
11	John Hunter Children's Hospital	Newcastle		Australia
12	Children's Hospital at Westmead	Sydney		Australia
13	Sydney Children's Hospital at Randwick	Sydney		Australia
14	Perth Children's Hospital	West Perth		Australia
15	Universitair Ziekenhuis Children's Hospital	Brussels		Belgium
16	UZ Leuven - Gasthuisberg Ziekenhuis	Leuven		Belgium
17	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H3V4
18	Hospital for Sick Kids	Toronto	Ontario	Canada	M5G1X8
19	Copenhagen University Hospital Rigshospitalet	Copenhagen		Denmark
20	Hospice Civils de Lyon	Lyon		France
21	Hospital Robert Debre	Paris		France
22	Bambini Gesu Children's Hospital	Roma		Italy	00165
23	Ospedale Civile Maggiore	Verona		Italy	37126
24	Sophia Children's Hospital at Erasmus Medical Centre	Rotterdam		Netherlands
25	Hospital Universitari Vall d'Hebron	Barcelona		Spain

Sponsors and Collaborators

• University of Washington, the Collaborative Health Studies Coordinating Center
• Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Harm Tiddens, MD, PhD, Erasmus Medical Centre, Rotterdam
• Principal Investigator: Stephen Stick, MD, PhD, Telethon Kids Institute, Perth
• Principal Investigator: Margaret Rosenfeld, MD, MPH, Seattle Children's Hospital, Seattle
• Principal Investigator: Stephanie Davis, MD, Indiana University, Indianapolis
• Principal Investigator: Felix Ratjen, MD, PhD, FRCPC, The Hospital for Sick Children

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: University of Washington, the Collaborative Health Studies Coordinating Center
• ClinicalTrials.gov Identifier: NCT02950883
• Other Study ID Numbers: SHIP002
• First Posted: Nov 1, 2016
• Last Update Posted: Aug 10, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Washington, the Collaborative Health Studies Coordinating Center: Cystic Fibrosis; Hypertonic Saline; Inhaled Saline; Digestive System Diseases; Genetic Diseases, Inborn; Lung Diseases; Pancreatic Diseases; Pathologic Processes; Respiratory Tract Diseases; Computed Tomography (CT)
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

No Results Posted as of Aug 10, 2021