Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial

SHIP Study Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Inhaled hypertonic saline enhances mucociliary clearance, improves lung function, and reduces pulmonary exacerbations in people with cystic fibrosis older than age 6 years. We aimed to assess the effect of inhaled hypertonic saline on the lung clearance index (LCI2·5)—a measure of ventilation inhomogeneity—in children aged 3–6 years with cystic fibrosis. Methods: The Saline Hypertonic in Preschoolers (SHIP) Study was a randomised, double-blind, placebo-controlled trial at 25 cystic fibrosis centres in Canada and the USA. Eligible participants were aged 36–72 months; had a confirmed diagnosis of cystic fibrosis; were able to comply with medication use, study visits, and study procedures; and were able to complete at least two technically acceptable trials of multiple breath washout (MBW). Participants were randomly assigned (1:1) via a web-based data entry system that confirmed enrolment eligibility to inhaled 7% hypertonic saline or 0·9% isotonic saline nebulised twice daily (for no more than 15 min per dose) for 48 weeks. Permuted block randomisation was done separately for participants aged 36–54 months and those aged 55–72 months to ensure approximate balance by treatment group in the two age groups. The primary endpoint was the change in the LCI2·5 measured by nitrogen MBW from baseline to week 48. All study sites were trained and certified in MBW. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT02378467. Findings: Between April 21, 2015, and Aug 4, 2017, 150 participants were enrolled and randomly assigned, 76 to the hypertonic saline group and 74 to the isotonic saline group. Overall 89% of the MBW tests produced acceptable data. At 48 weeks, treatment with hypertonic saline was associated with a significant decrease (ie, improvement) in LCI2·5 compared with isotonic saline (mean treatment effect −0·63 LCI2·5 units [95% CI −1·10 to −0·15]; p=0·010). Six participants in the hypertonic saline group had ten serious adverse events and eight participants in the isotonic saline group had nine serious adverse events. The serious adverse events reported were cough (two patients [3%] in the hypertonic saline group vs three [4%] in the isotonic saline group), gastrostomy tube placement or rupture (two [3%] vs one [1%]), upper gastrointestinal disorders (one [1%] vs two [3%]), distal intestinal obstruction syndrome (one [1%] vs one [1%]), and decreased pulmonary function (none vs one [1%]). None of these serious adverse events was judged to be treatment related. Interpretation: Inhaled hypertonic saline improved the LCI2·5 in children aged 3–6 years, and could be a suitable early intervention in cystic fibrosis. Funding: Cystic Fibrosis Foundation.

Original languageEnglish (US)
Pages (from-to)802-809
Number of pages8
JournalThe Lancet Respiratory Medicine
Volume7
Issue number9
DOIs
StatePublished - Sep 2019
Externally publishedYes

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Preschool Children
Cystic Fibrosis
Placebos
Lung
Mucociliary Clearance
Intention to Treat Analysis
Breath Tests
Gastrostomy
Intestinal Obstruction
Therapeutics
Random Allocation
Cough
Information Systems
Canada
Ventilation
Rupture
Nitrogen
Age Groups

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

@article{a2dbcccd0a67485b900b727ff85c06e7,
title = "Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial",
abstract = "Background: Inhaled hypertonic saline enhances mucociliary clearance, improves lung function, and reduces pulmonary exacerbations in people with cystic fibrosis older than age 6 years. We aimed to assess the effect of inhaled hypertonic saline on the lung clearance index (LCI2·5)—a measure of ventilation inhomogeneity—in children aged 3–6 years with cystic fibrosis. Methods: The Saline Hypertonic in Preschoolers (SHIP) Study was a randomised, double-blind, placebo-controlled trial at 25 cystic fibrosis centres in Canada and the USA. Eligible participants were aged 36–72 months; had a confirmed diagnosis of cystic fibrosis; were able to comply with medication use, study visits, and study procedures; and were able to complete at least two technically acceptable trials of multiple breath washout (MBW). Participants were randomly assigned (1:1) via a web-based data entry system that confirmed enrolment eligibility to inhaled 7{\%} hypertonic saline or 0·9{\%} isotonic saline nebulised twice daily (for no more than 15 min per dose) for 48 weeks. Permuted block randomisation was done separately for participants aged 36–54 months and those aged 55–72 months to ensure approximate balance by treatment group in the two age groups. The primary endpoint was the change in the LCI2·5 measured by nitrogen MBW from baseline to week 48. All study sites were trained and certified in MBW. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT02378467. Findings: Between April 21, 2015, and Aug 4, 2017, 150 participants were enrolled and randomly assigned, 76 to the hypertonic saline group and 74 to the isotonic saline group. Overall 89{\%} of the MBW tests produced acceptable data. At 48 weeks, treatment with hypertonic saline was associated with a significant decrease (ie, improvement) in LCI2·5 compared with isotonic saline (mean treatment effect −0·63 LCI2·5 units [95{\%} CI −1·10 to −0·15]; p=0·010). Six participants in the hypertonic saline group had ten serious adverse events and eight participants in the isotonic saline group had nine serious adverse events. The serious adverse events reported were cough (two patients [3{\%}] in the hypertonic saline group vs three [4{\%}] in the isotonic saline group), gastrostomy tube placement or rupture (two [3{\%}] vs one [1{\%}]), upper gastrointestinal disorders (one [1{\%}] vs two [3{\%}]), distal intestinal obstruction syndrome (one [1{\%}] vs one [1{\%}]), and decreased pulmonary function (none vs one [1{\%}]). None of these serious adverse events was judged to be treatment related. Interpretation: Inhaled hypertonic saline improved the LCI2·5 in children aged 3–6 years, and could be a suitable early intervention in cystic fibrosis. Funding: Cystic Fibrosis Foundation.",
author = "{SHIP Study Group} and Felix Ratjen and Davis, {Stephanie D.} and Sanja Stanojevic and Kronmal, {Richard A.} and {Hinckley Stukovsky}, {Karen D.} and Neal Jorgensen and Margaret Rosenfeld and Gwen Kerby and Carol Kopecky and Meg Anthony and Peter Mogayzel and Doug Walker and Britany Zeglin and Wynton Hoover and Heather Hathorne and Katie Slaten and Dorkin, {Henry (Hank)} and Robert Fowler and Fenton, {Cole (Nicolas)} and Monica Ulles and Danielle Goetz and Nadine Caci and Beth Cahill and Christine Roach and George Retsch-Bogart and Robin Johnson and Rose Cunnion and Susanna McColley and Steven Ward and Emily Bell and Gary McPhail and Kimberly Keller and Kelly Thornton and Ashlee Parsons and James Chmiel and Cindy Schaefer and Megan Tribout and Brittany Consiglio and Heather Tribout and Karen McCoy and Terri Johnson and Patti Olson and Laura Raterman and Peter Hiatt and Betty Walker and Nicoline Schaap and Miriam Davis and Stephanie Davis and Charles Clem and Lisa Bendy",
year = "2019",
month = "9",
doi = "10.1016/S2213-2600(19)30187-0",
language = "English (US)",
volume = "7",
pages = "802--809",
journal = "The Lancet Respiratory Medicine",
issn = "2213-2600",
publisher = "Elsevier Limited",
number = "9",

}

TY - JOUR

T1 - Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP)

T2 - a multicentre, randomised, double-blind, placebo-controlled trial

AU - SHIP Study Group

AU - Ratjen, Felix

AU - Davis, Stephanie D.

AU - Stanojevic, Sanja

AU - Kronmal, Richard A.

AU - Hinckley Stukovsky, Karen D.

AU - Jorgensen, Neal

AU - Rosenfeld, Margaret

AU - Kerby, Gwen

AU - Kopecky, Carol

AU - Anthony, Meg

AU - Mogayzel, Peter

AU - Walker, Doug

AU - Zeglin, Britany

AU - Hoover, Wynton

AU - Hathorne, Heather

AU - Slaten, Katie

AU - Dorkin, Henry (Hank)

AU - Fowler, Robert

AU - Fenton, Cole (Nicolas)

AU - Ulles, Monica

AU - Goetz, Danielle

AU - Caci, Nadine

AU - Cahill, Beth

AU - Roach, Christine

AU - Retsch-Bogart, George

AU - Johnson, Robin

AU - Cunnion, Rose

AU - McColley, Susanna

AU - Ward, Steven

AU - Bell, Emily

AU - McPhail, Gary

AU - Keller, Kimberly

AU - Thornton, Kelly

AU - Parsons, Ashlee

AU - Chmiel, James

AU - Schaefer, Cindy

AU - Tribout, Megan

AU - Consiglio, Brittany

AU - Tribout, Heather

AU - McCoy, Karen

AU - Johnson, Terri

AU - Olson, Patti

AU - Raterman, Laura

AU - Hiatt, Peter

AU - Walker, Betty

AU - Schaap, Nicoline

AU - Davis, Miriam

AU - Davis, Stephanie

AU - Clem, Charles

AU - Bendy, Lisa

PY - 2019/9

Y1 - 2019/9

N2 - Background: Inhaled hypertonic saline enhances mucociliary clearance, improves lung function, and reduces pulmonary exacerbations in people with cystic fibrosis older than age 6 years. We aimed to assess the effect of inhaled hypertonic saline on the lung clearance index (LCI2·5)—a measure of ventilation inhomogeneity—in children aged 3–6 years with cystic fibrosis. Methods: The Saline Hypertonic in Preschoolers (SHIP) Study was a randomised, double-blind, placebo-controlled trial at 25 cystic fibrosis centres in Canada and the USA. Eligible participants were aged 36–72 months; had a confirmed diagnosis of cystic fibrosis; were able to comply with medication use, study visits, and study procedures; and were able to complete at least two technically acceptable trials of multiple breath washout (MBW). Participants were randomly assigned (1:1) via a web-based data entry system that confirmed enrolment eligibility to inhaled 7% hypertonic saline or 0·9% isotonic saline nebulised twice daily (for no more than 15 min per dose) for 48 weeks. Permuted block randomisation was done separately for participants aged 36–54 months and those aged 55–72 months to ensure approximate balance by treatment group in the two age groups. The primary endpoint was the change in the LCI2·5 measured by nitrogen MBW from baseline to week 48. All study sites were trained and certified in MBW. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT02378467. Findings: Between April 21, 2015, and Aug 4, 2017, 150 participants were enrolled and randomly assigned, 76 to the hypertonic saline group and 74 to the isotonic saline group. Overall 89% of the MBW tests produced acceptable data. At 48 weeks, treatment with hypertonic saline was associated with a significant decrease (ie, improvement) in LCI2·5 compared with isotonic saline (mean treatment effect −0·63 LCI2·5 units [95% CI −1·10 to −0·15]; p=0·010). Six participants in the hypertonic saline group had ten serious adverse events and eight participants in the isotonic saline group had nine serious adverse events. The serious adverse events reported were cough (two patients [3%] in the hypertonic saline group vs three [4%] in the isotonic saline group), gastrostomy tube placement or rupture (two [3%] vs one [1%]), upper gastrointestinal disorders (one [1%] vs two [3%]), distal intestinal obstruction syndrome (one [1%] vs one [1%]), and decreased pulmonary function (none vs one [1%]). None of these serious adverse events was judged to be treatment related. Interpretation: Inhaled hypertonic saline improved the LCI2·5 in children aged 3–6 years, and could be a suitable early intervention in cystic fibrosis. Funding: Cystic Fibrosis Foundation.

AB - Background: Inhaled hypertonic saline enhances mucociliary clearance, improves lung function, and reduces pulmonary exacerbations in people with cystic fibrosis older than age 6 years. We aimed to assess the effect of inhaled hypertonic saline on the lung clearance index (LCI2·5)—a measure of ventilation inhomogeneity—in children aged 3–6 years with cystic fibrosis. Methods: The Saline Hypertonic in Preschoolers (SHIP) Study was a randomised, double-blind, placebo-controlled trial at 25 cystic fibrosis centres in Canada and the USA. Eligible participants were aged 36–72 months; had a confirmed diagnosis of cystic fibrosis; were able to comply with medication use, study visits, and study procedures; and were able to complete at least two technically acceptable trials of multiple breath washout (MBW). Participants were randomly assigned (1:1) via a web-based data entry system that confirmed enrolment eligibility to inhaled 7% hypertonic saline or 0·9% isotonic saline nebulised twice daily (for no more than 15 min per dose) for 48 weeks. Permuted block randomisation was done separately for participants aged 36–54 months and those aged 55–72 months to ensure approximate balance by treatment group in the two age groups. The primary endpoint was the change in the LCI2·5 measured by nitrogen MBW from baseline to week 48. All study sites were trained and certified in MBW. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT02378467. Findings: Between April 21, 2015, and Aug 4, 2017, 150 participants were enrolled and randomly assigned, 76 to the hypertonic saline group and 74 to the isotonic saline group. Overall 89% of the MBW tests produced acceptable data. At 48 weeks, treatment with hypertonic saline was associated with a significant decrease (ie, improvement) in LCI2·5 compared with isotonic saline (mean treatment effect −0·63 LCI2·5 units [95% CI −1·10 to −0·15]; p=0·010). Six participants in the hypertonic saline group had ten serious adverse events and eight participants in the isotonic saline group had nine serious adverse events. The serious adverse events reported were cough (two patients [3%] in the hypertonic saline group vs three [4%] in the isotonic saline group), gastrostomy tube placement or rupture (two [3%] vs one [1%]), upper gastrointestinal disorders (one [1%] vs two [3%]), distal intestinal obstruction syndrome (one [1%] vs one [1%]), and decreased pulmonary function (none vs one [1%]). None of these serious adverse events was judged to be treatment related. Interpretation: Inhaled hypertonic saline improved the LCI2·5 in children aged 3–6 years, and could be a suitable early intervention in cystic fibrosis. Funding: Cystic Fibrosis Foundation.

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