Clinical trial NCT00709280: Infant Study of Inhaled Saline in Cystic Fibrosis
Official title: Infant Study of Inhaled Saline in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
hypertonic saline
inhaled saline
Lead sponsor: CF Therapeutics Development Network Coordinating Center
Sponsor class: NETWORK
Collaborators: name: Cystic Fibrosis Foundation
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-07-03
Enrollment: 321
Sex: ALL
Minimum age (years): 4
Maximum age (years): 59
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 7% hypertonic saline (HS) is an effective and safe therapy in infants and young children with CF.

Detailed description: A growing body of evidence supports the importance of intervention in Cystic Fibrosis (CF) lung disease during infancy and early childhood, in order to potentially delay or prevent irreversible lung disease. Yet, aside from antimicrobial therapies, the CF community has no clinical trial evidence base with which to guide pulmonary therapies in children \<6 years of age. Hypertonic Saline (HS) is the most attractive chronic maintenance therapy to investigate in these young 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.

This study is a randomized, parallel group, controlled trial to assess the efficacy and safety of 7% HS inhaled twice daily for 48 weeks among young children with CF 4 to \< 60 months of age at enrollment. The primary hypothesis is that, compared to isotonic saline (IS), HS will decrease the number of protocol-defined pulmonary exacerbations during the 48 week treatment period. The results of the proposed trial may for the first time provide evidence for early initiation of HS, which, by improving mucociliary clearance, may delay or hinder the cycle of infection and inflammation responsible for progressive airway damage in CF lung disease.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND either: (a) A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis or (b) A genotype with two identifiable CF-causing mutations
* Informed consent by parent or legal guardian
* Age 4 months to \< 60 months at Enrollment visit. If participating in Infant Pulmonary Function testing (selected sites), age 4 months to \< 16 months at Enrollment visit.
* Ability to comply with medication use, study visits, and study procedures as judged by the site investigator

Exclusion Criteria:

* Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding Enrollment visit
* Acute wheezing at Enrollment visit (prior to HS test dose), or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
* Oxygen saturation \< 95% (\< 90% in centers located above 4000 feet elevation) at Enrollment visit (prior to HS test dose) or at Infant PFT visit (prior to infant pulmonary function testing), as applicable
* Other major organ dysfunction, excluding pancreatic dysfunction
* Physical findings that would compromise the safety of the subject or the quality of the study data as determined by the site investigator
* Investigational drug use within 30 days prior to Enrollment visit, or within 30 days prior to Infant PFT visit as applicable
* Treatment with inhaled hypertonic saline at any concentration within 30 days of Enrollment visit, or within 30 days prior to Infant PFT visit as applicable
* Chronic lung disease not related to CF
* Intolerance of test dose of HS at Enrollment visit
* A sibling that has been randomized and is still enrolled in ISIS002

Additional Exclusion Criteria for Participation in Infant Pulmonary Function Testing:

* History of adverse reaction to sedation
* Clinically significant upper airway obstruction as determined by the Site Investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea)
* Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy
* Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 2 weeks preceding visit

Primary outcomes:
measure: The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS
timeFrame: during the 48 week treatment period
Secondary outcomes:
measure: Symptoms by parent home questionnaire administered weekly
timeFrame: during the 48 week treatment period
measure: Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly
timeFrame: over the 48 week treatment period
measure: Standardized cough score assessed at study visits
timeFrame: during the 48 week treatment period
measure: Change in weight, height, resting respiratory rate, and room air oxygen saturation
timeFrame: over the 48 week treatment period
measure: Among participants from whom Pseudomonas aeruginosa (Pa) and other CF pathogens were not isolated from respiratory cultures prior to enrollment, the proportion from whom these organisms are isolated from clinically collected respiratory cultures
timeFrame: measured at baseline and at 48 weeks
measure: Pulmonary function indices measured at baseline and 48 weeks in infants 4 to 15 months of age at enrollment participating in infant pulmonary function testing (N = 100, selected sites)
timeFrame: over the 48 week treatment period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University / Lucile S. Packard Children's Hospital
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Chicago
country: United States
facility: Children's Memorial Hospital and Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University / Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan / C.S. Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital, Pulmonary Division
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia - Pediatric Respiratory Medicine
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital & Regional Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Stephanie Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital and Regional Medical Center
name: Margaret Rosenfeld, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto Hospital for Sick Children
name: Felix Ratjen, MD, PhD
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: Subbarao P, Stanojevic S, Brown M, Jensen R, Rosenfeld M, Davis S, Brumback L, Gustafsson P, Ratjen F. Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline. Am J Respir Crit Care Med. 2013 Aug 15;188(4):456-60. doi: 10.1164/rccm.201302-0219OC.