SHIP: Saline Hypertonic in Preschoolers

Sponsor

University of Washington, the Collaborative Health Studies Coordinating Center (Other)

Overall Status

Completed

CT.gov ID

NCT02378467

Collaborator

Cystic Fibrosis Foundation (Other)

150

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

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 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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: 7% Hypertonic Saline (HS) Drug: 0.9% Isotonic Saline (IS)	N/A

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Saline Hypertonic in Preschoolers

Actual Study Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Aug 31, 2018

Actual Study Completion Date :

Aug 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Treatment Group 7% Hypertonic Saline administered via inhalation twice daily for 48 weeks	Drug: 7% Hypertonic Saline (HS) 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 Names: Hyper-Sal™, inhaled saline
Active Comparator: Control Group 0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks	Drug: 0.9% Isotonic Saline (IS) 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 Names: Normal saline

Arm

Intervention/Treatment

Experimental: Active Treatment Group

7% Hypertonic Saline administered via inhalation twice daily for 48 weeks

Drug: 7% Hypertonic Saline (HS)

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 Names:

Hyper-Sal™, inhaled saline

Active Comparator: Control Group

0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks

Drug: 0.9% Isotonic Saline (IS)

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 Names:

Normal saline

Outcome Measures

Primary Outcome Measures

Change in Lung Clearance Index (LCI) [48 weeks]
Change in Lung Clearance Index (LCI) from baseline to 48 weeks measured by N2 Multiple Breath Washout (MBW) between subjects randomized to HS and IS.

Secondary Outcome Measures

Change in Forced Expiratory Volume (FEV) [48 weeks]
Change in FEV 0.75 measured by preschool spirometry between subjects randomized to HS and IS.
Pulmonary exacerbation rate [48 weeks]
Protocol defined pulmonary exacerbation rate.
Health-related quality of life [48 weeks]
Health-related quality of life as measured by the modified parent-reported Cystic Fibrosis Questionnaire-Revised (CFQ-R) for preschoolers.
Respiratory Signs [48 weeks]
Parent observation of respiratory signs as measured by the Cystic Fibrosis Respiratory Sign Diary for ages 0-6 (CFRSD0-6).
Respiratory Pathogen Rate [48 weeks]
Rates of treatment emergent CF respiratory pathogens from clinical respiratory cultures.

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 5 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of CF as evidenced by one or more clinical feature consistent with the CF phenotype or positive CF newborn screen AND one or more of the following criteria:
A documented sweat chloride ≥ 60 milliequivalents of solute per litre (mEq/L) by quantitative pilocarpine iontophoresis (QPIT)
A documented genotype with two disease-causing mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene
Informed consent by parent or legal guardian
Age ≥ 36 months and ≤72 months at Screening visit
Ability to comply with medication use, study visits and study procedures as judged by the site investigator
Ability to perform technically acceptable MBW measurements at the screening and enrollment visits

Exclusion Criteria:

Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding Screening or Enrollment visit
Acute wheezing at Screening or Enrollment visit
Oxygen saturation < 95% (<90% in centers located above 4000 feet elevation) at Screening or Enrollment visit
Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator
Investigational drug use within 30 days prior to Screening or Enrollment visit
Treatment with inhaled hypertonic saline at any concentration within 30 days prior to Screening or Enrollment visit
Chronic lung disease not related to CF
Inability to tolerate first dose of study treatment at the Enrollment visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama-Birmingham: Pulmonary, Allergy and Critical Care Medicine	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	Children's Hospital of Colorado	Aurora	Colorado	United States	80045
4	Nemours Children's Hospital	Orlando	Florida	United States	32827
5	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
6	Riley Hospital for Children-Indiana U Med Center	Indianapolis	Indiana	United States	46202
7	University of Iowa, Department of Pediatrics	Iowa City	Iowa	United States	52242
8	Johns Hopkins University: Pediatric Pulmonary	Baltimore	Maryland	United States	21287
9	Boston Children's Hospital	Boston	Massachusetts	United States	02115
10	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
11	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
12	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
13	Women & Children's Hospital of Buffalo	Buffalo	New York	United States	14222
14	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7217
15	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
16	Rainbow Babies Children's Hospital and Case Western Reserve University School of Medicine	Cleveland	Ohio	United States	44212
17	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
18	Oregon Health Sciences University	Portland	Oregon	United States	97239
19	Children's Hospital of Philadelphia, UPenn	Philadelphia	Pennsylvania	United States	19104
20	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
21	Texas Children's Hospital and Baylor College of Medicine	Houston	Texas	United States	77030
22	Seattle Children's Hospital	Seattle	Washington	United States	98105
23	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
24	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
25	Hospital for Sick Kids	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

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

Investigators

Principal Investigator: Stephanie Davis, MD, Indiana University
Principal Investigator: Richard A Kronmal, PhD, University of Washington
Principal Investigator: Felix Ratjen, MD, PhD, FRCPC, Hospital for Sick Kids, Toronto
Principal Investigator: Margaret Rosenfeld, MD, MPH, Seattle Children's Hospital