Cystic FibrosisSHIPNCT02378467
Saline Hypertonic in Preschoolers
A study testing 7% Hypertonic Saline (HS) and 0.9% Isotonic Saline (IS) in people with Cystic Fibrosis, run by University of Washington, the Collaborative Health Studies Coordinating Center at 25 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 5 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- 7% Hypertonic Saline (HS) and 0.9% Isotonic Saline (IS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 25 sitesin 2 countries
- Study dates
- 1 Mar 2015to 31 Aug 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
25 sites in 2 countries.
25 sites in 2 countries
United States23 sites
Children's Hospital of Colorado
Aurora, Colorado, 80045
Johns Hopkins University: Pediatric Pulmonary
Baltimore, Maryland, 21287
University of Alabama-Birmingham: Pulmonary, Allergy and Critical Care Medicine
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
Women & Children's Hospital of Buffalo
Buffalo, New York, 14222
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7217
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies Children's Hospital and Case Western Reserve University School of Medicine
Cleveland, Ohio, 44212
Nationwide Children's Hospital
Columbus, Ohio, 43205
Texas Children's Hospital and Baylor College of Medicine
Houston, Texas, 77030
Riley Hospital for Children-Indiana U Med Center
Indianapolis, Indiana, 46202
University of Iowa, Department of Pediatrics
Iowa City, Iowa, 52242
Children's Mercy Hospital
Kansas City, Missouri, 64108
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Nemours Children's Hospital
Orlando, Florida, 32827
Stanford University
Palo Alto, California, 94304
Children's Hospital of Philadelphia, UPenn
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health Sciences University
Portland, Oregon, 97239
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Canada2 sites
Hospital for Sick Kids
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
About this study
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.
Read the 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).
- Conditions
- Cystic Fibrosis
- Being tested
- 7% Hypertonic Saline (HS), 0.9% Isotonic Saline (IS)
- Keywords
- Cystic Fibrosis, Hypertonic Saline, Inhaled Saline, Digestive System Diseases, Genetic Diseases, Inborn, Lung Diseases, Pancreatic Diseases, Pathologic Processes, Respiratory Tract Diseases
- Medical subject headings
- Cystic Fibrosis, Digestive System Diseases, Genetic Diseases, Inborn, Lung Diseases, Pancreatic Diseases, Pathologic Processes, Respiratory Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
7% Hypertonic Saline (HS)Drug
Also called Hyper-Sal™, inhaled saline
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.
0.9% Isotonic Saline (IS)Drug
Also called Normal saline
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.
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment Group | Experimental | 7% Hypertonic Saline administered via inhalation twice daily for 48 weeks Receives: Drug: 7% Hypertonic Saline (HS) |
| Control Group | Active comparator | 0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks Receives: Drug: 0.9% Isotonic Saline (IS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Lung Clearance Index (LCI)
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.
Measured: 48 weeks
Secondary outcomes (5)
Change in Forced Expiratory Volume (FEV)
Change in FEV 0.75 measured by preschool spirometry between subjects randomized to HS and IS.
Measured: 48 weeks
Pulmonary exacerbation rate
Protocol defined pulmonary exacerbation rate.
Measured: 48 weeks
Health-related quality of life
Health-related quality of life as measured by the modified parent-reported Cystic Fibrosis Questionnaire-Revised (CFQ-R) for preschoolers.
Measured: 48 weeks
Respiratory Signs
Parent observation of respiratory signs as measured by the Cystic Fibrosis Respiratory Sign Diary for ages 0-6 (CFRSD0-6).
Measured: 48 weeks
Respiratory Pathogen Rate
Rates of treatment emergent CF respiratory pathogens from clinical respiratory cultures.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study start1 Mar 2015
- Primary completion31 Aug 2018
- Study completion31 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington, the Collaborative Health Studies Coordinating Center
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Stephanie Davis, MD, Principal investigator, Indiana UniversityRichard A Kronmal, PhD, Principal investigator, University of WashingtonFelix Ratjen, MD, PhD, FRCPC, Principal investigator, Hospital for Sick Kids, TorontoMargaret Rosenfeld, MD, MPH, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02378467
- Sponsor's protocol ID
- SHIP001
- Acronym
- SHIP
- Status last verified
- Dec 2019
- First submitted
- 27 Feb 2015
- Last updated
- 14 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R, Davis SD; ISIS Study Group. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 2012 Jun 6;307(21):2269-77. doi: 10.1001/jama.2012.5214.
PubMed 22610452Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010 May;65(5):379-83. doi: 10.1136/thx.2009.125831.
PubMed 20435858Ratjen F, Davis SD, Stanojevic S, Kronmal RA, Hinckley Stukovsky KD, Jorgensen N, Rosenfeld M; SHIP Study Group. Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2019 Sep;7(9):802-809. doi: 10.1016/S2213-2600(19)30187-0. Epub 2019 Jun 6.
PubMed 31178421
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Saline Hypertonic in Preschoolers
- ClinicalTrials.gov ID
- NCT02378467
- Acronym / sponsor ID
- SHIP / SHIP001
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Hypertonic Saline, Inhaled Saline, Digestive System Diseases, Genetic Diseases, Inborn, Lung Diseases, Pancreatic Diseases, Pathologic Processes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of Washington, the Collaborative Health Studies Coordinating CenterUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- 1 Mar 2015 (actual)
- Primary completion
- 31 Aug 2018 (actual)
- Study completion
- 31 Aug 2018 (actual)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Treatment Group | Experimental | Drug: 7% Hypertonic Saline (HS)7% Hypertonic Saline administered via inhalation twice daily for 48 weeks |
| Control Group | Active comparator | Drug: 0.9% Isotonic Saline (IS)0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks |
Who may qualify
- Ages
- 3 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 7% Hypertonic Saline (HS)Also: Hyper-Sal™, inhaled salineAdministered 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. | Drug | Active Treatment Group |
| 0.9% Isotonic Saline (IS)Also: Normal salineAdministered 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. | Drug | Control Group |
Primary outcome
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.
5 secondary outcomes
Change in Forced Expiratory Volume (FEV)
Time frame: 48 weeks
Pulmonary exacerbation rate
Time frame: 48 weeks
Health-related quality of life
Time frame: 48 weeks
Respiratory Signs
Time frame: 48 weeks
Respiratory Pathogen Rate
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
- Background: PubMed 22610452Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R, Davis SD; ISIS Study Group. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 2012 Jun 6;307(21):2269-77. doi: 10.1001/jama.2012.5214.
- Background: PubMed 20435858Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010 May;65(5):379-83. doi: 10.1136/thx.2009.125831.
- Results publication: PubMed 31178421Ratjen F, Davis SD, Stanojevic S, Kronmal RA, Hinckley Stukovsky KD, Jorgensen N, Rosenfeld M; SHIP Study Group. Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2019 Sep;7(9):802-809. doi: 10.1016/S2213-2600(19)30187-0. Epub 2019 Jun 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie Davis, MD principal investigator
Indiana University
Richard A Kronmal, PhD principal investigator
University of Washington
Felix Ratjen, MD, PhD, FRCPC principal investigator
Hospital for Sick Kids, Toronto
25 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 7% Hypertonic Saline (HS) and 0.9% Isotonic Saline (IS) in people with Cystic Fibrosis, run by University of Washington, the Collaborative Health Studies Coordinating Center at 25 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Lung Clearance Index (LCI) (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02378467, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2020.