Infant Study of Inhaled Saline in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— ISIS  

Official title:

Infant Study of Inhaled Saline in Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00709280
• Other study ID #: ISIS002
• Secondary ID: U01HL092931U01HL
• Status: Completed
• Phase: N/A
• First received: July 1, 2008
• Last updated: February 11, 2013
• Start date: April 2009
• Est. completion date: November 2011

Study information

• Verified date: February 2013
• Source: CF Therapeutics Development Network Coordinating Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 321
• Est. completion date: November 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 59 Months

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• 7% Hypertonic Saline (HS)
Administered via inhalation twice daily for 48 ± 4 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Pro Neb compressor.
• 0.9% Isotonic Saline (IS)
Administered via inhalation twice daily for 48 ± 4 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI Pro Neb compressor.

Locations

Country	Name	City	State
Canada	Hospital For Sick Children	Toronto	Ontario
Canada	BC Children's Hospital	Vancouver	British Columbia
United States	University of Michigan / C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	The Children's Hospital	Aurora	Colorado
United States	Johns Hopkins University / Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Virginia - Pediatric Respiratory Medicine	Charlottesville	Virginia
United States	Children's Memorial Hospital and Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital, Pulmonary Division	Columbus	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	University of Nebraska	Omaha	Nebraska
United States	Stanford University / Lucile S. Packard Children's Hospital	Palo Alto	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Utah	Salt Lake City	Utah
United States	Children's Hospital & Regional Medical Center	Seattle	Washington
United States	Cardinal Glennon Children's Hospital	St. Louis	Missouri
United States	Washington University in St. Louis	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (3)

Lead Sponsor	Collaborator
CF Therapeutics Development Network Coordinating Center	Cystic Fibrosis Foundation Therapeutics, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS		during the 48 week treatment period
Secondary	Symptoms by parent home questionnaire administered weekly		during the 48 week treatment period
Secondary	Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly		over the 48 week treatment period
Secondary	Standardized cough score assessed at study visits		during the 48 week treatment period
Secondary	Change in weight, height, resting respiratory rate, and room air oxygen saturation		over the 48 week treatment period
Secondary	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		measured at baseline and at 48 weeks
Secondary	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)		over the 48 week treatment period