Clinical trial NCT02378467: Saline Hypertonic in Preschoolers
Official title: Saline Hypertonic in Preschoolers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Hypertonic Saline
Inhaled Saline
Digestive System Diseases
Genetic Diseases, Inborn
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Lead sponsor: University of Washington, the Collaborative Health Studies Coordinating Center
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2015-03-04
Enrollment: 150
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in Lung Clearance Index (LCI)
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in Forced Expiratory Volume (FEV)
timeFrame: 48 weeks
measure: Pulmonary exacerbation rate
timeFrame: 48 weeks
measure: Health-related quality of life
timeFrame: 48 weeks
measure: Respiratory Signs
timeFrame: 48 weeks
measure: Respiratory Pathogen Rate
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama-Birmingham: Pulmonary, Allergy and Critical Care Medicine
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children-Indiana U Med Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa, Department of Pediatrics
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University: Pediatric Pulmonary
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Women & Children's Hospital of Buffalo
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies Children's Hospital and Case Western Reserve University School of Medicine
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia, UPenn
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital and Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Hospital for Sick Kids
state: Ontario
Study officials:
affiliation: Indiana University
name: Stephanie Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Richard A Kronmal, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital for Sick Kids, Toronto
name: Felix Ratjen, MD, PhD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Margaret Rosenfeld, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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. Lancet Respir Med. 2019 Sep;7(9):802-809. doi: 10.1016/S2213-2600(19)30187-0. Epub 2019 Jun 6.