Saline Hypertonic in Preschoolers (SHIP)

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 5 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active Treatment Group
7% Hypertonic Saline administered via inhalation twice daily for 48 weeks
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Lung Clearance Index (LCI)
Time Frame: 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.
48 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Margaret Rosenfeld, MD, MPH, Seattle Children's Hospital
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2015

Primary Completion (Actual)

August 31, 2018

Study Completion (Actual)

August 31, 2018

Study Registration Dates

First Submitted

February 27, 2015

First Submitted That Met QC Criteria

March 3, 2015

First Posted (Estimate)

March 4, 2015

Study Record Updates

Last Update Posted (Actual)

January 14, 2020

Last Update Submitted That Met QC Criteria

January 10, 2020

Last Verified

December 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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