Saline Hypertonic in Preschoolers

Cystic Fibrosis Clinical Trial

— SHIP  

Official title:

Saline Hypertonic in Preschoolers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02378467
• Other study ID #: SHIP001
• Status: Completed
• Phase: N/A
• Start date: March 1, 2015
• Est. completion date: August 31, 2018

Study information

• Verified date: December 2019
• Source: University of Washington, the Collaborative Health Studies Coordinating Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 31, 2018
• Est. primary completion date: August 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Hospital for Sick Kids	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Johns Hopkins University: Pediatric Pulmonary	Baltimore	Maryland
United States	University of Alabama-Birmingham: Pulmonary, Allergy and Critical Care Medicine	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Women & Children's Hospital of Buffalo	Buffalo	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Rainbow Babies Children's Hospital and Case Western Reserve University School of Medicine	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Texas Children's Hospital and Baylor College of Medicine	Houston	Texas
United States	Riley Hospital for Children-Indiana U Med Center	Indianapolis	Indiana
United States	University of Iowa, Department of Pediatrics	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	Nemours Children's Hospital	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia, UPenn	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Amin 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. — View Citation

Ratjen 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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	48 weeks
Secondary	Change in Forced Expiratory Volume (FEV)	Change in FEV 0.75 measured by preschool spirometry between subjects randomized to HS and IS.	48 weeks
Secondary	Pulmonary exacerbation rate	Protocol defined pulmonary exacerbation rate.	48 weeks
Secondary	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.	48 weeks
Secondary	Respiratory Signs	Parent observation of respiratory signs as measured by the Cystic Fibrosis Respiratory Sign Diary for ages 0-6 (CFRSD0-6).	48 weeks
Secondary	Respiratory Pathogen Rate	Rates of treatment emergent CF respiratory pathogens from clinical respiratory cultures.	48 weeks