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Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS)

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
7% Hypertonic Saline (HS)
0.9% Isotonic Saline (IS)
Sponsored by
CF Therapeutics Development Network Coordinating Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, hypertonic saline, inhaled saline

Eligibility Criteria

4 Months - 59 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Phoenix Children's Hospital
  • Stanford University / Lucile S. Packard Children's Hospital
  • The Children's Hospital
  • Children's Memorial Hospital and Northwestern University
  • Riley Hospital for Children
  • University of Iowa Hospitals and Clinics
  • University of Louisville
  • Johns Hopkins University / Johns Hopkins Hospital
  • University of Michigan / C.S. Mott Children's Hospital
  • Children's Hospitals and Clinics of Minnesota
  • Cardinal Glennon Children's Hospital
  • Washington University in St. Louis
  • University of Nebraska
  • Women and Children's Hospital of Buffalo
  • University of Rochester Medical Center
  • SUNY Upstate Medical University
  • University of North Carolina
  • Cincinnati Children's Hospital Medical Center
  • Nationwide Children's Hospital, Pulmonary Division
  • The Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Texas Children's Hospital
  • University of Utah
  • University of Virginia - Pediatric Respiratory Medicine
  • Children's Hospital & Regional Medical Center
  • University of Wisconsin
  • Children's Hospital of Wisconsin
  • BC Children's Hospital
  • Hospital For Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Active treatment group

Control group

Arm Description

7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks

0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks

Outcomes

Primary Outcome Measures

The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS

Secondary Outcome Measures

Symptoms by parent home questionnaire administered weekly
Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly
Standardized cough score assessed at study visits
Change in weight, height, resting respiratory rate, and room air oxygen saturation
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
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)

Full Information

First Posted
July 1, 2008
Last Updated
February 11, 2013
Sponsor
CF Therapeutics Development Network Coordinating Center
Collaborators
Cystic Fibrosis Foundation, National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00709280
Brief Title
Infant Study of Inhaled Saline in Cystic Fibrosis
Acronym
ISIS
Official Title
Infant Study of Inhaled Saline in Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CF Therapeutics Development Network Coordinating Center
Collaborators
Cystic Fibrosis Foundation, National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, hypertonic saline, inhaled saline

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
321 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active treatment group
Arm Type
Experimental
Arm Description
7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks
Intervention Type
Drug
Intervention Name(s)
7% Hypertonic Saline (HS)
Other Intervention Name(s)
Hyper-Sal™, inhaled saline
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
0.9% Isotonic Saline (IS)
Other Intervention Name(s)
Normal saline
Intervention Description
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.
Primary Outcome Measure Information:
Title
The rate of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics between subjects randomized to HS and IS
Time Frame
during the 48 week treatment period
Secondary Outcome Measure Information:
Title
Symptoms by parent home questionnaire administered weekly
Time Frame
during the 48 week treatment period
Title
Health-related quality of life as assessed by scores from Cystic Fibrosis Questionnaire-Revised Parent Report (CFQ-R), administered quarterly
Time Frame
over the 48 week treatment period
Title
Standardized cough score assessed at study visits
Time Frame
during the 48 week treatment period
Title
Change in weight, height, resting respiratory rate, and room air oxygen saturation
Time Frame
over the 48 week treatment period
Title
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
Time Frame
measured at baseline and at 48 weeks
Title
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)
Time Frame
over the 48 week treatment period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Months
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Davis, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Margaret Rosenfeld, MD, MPH
Organizational Affiliation
Children's Hospital and Regional Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Felix Ratjen, MD, PhD
Organizational Affiliation
University of Toronto Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Stanford University / Lucile S. Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
The Children's Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's Memorial Hospital and Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Johns Hopkins University / Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Michigan / C.S. Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University in St. Louis
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Women and Children's Hospital of Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14222
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital, Pulmonary Division
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15201
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
University of Virginia - Pediatric Respiratory Medicine
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Children's Hospital & Regional Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
BC Children's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
Hospital For Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
22610452
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.
Results Reference
result
PubMed Identifier
23742699
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.
Results Reference
derived

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Infant Study of Inhaled Saline in Cystic Fibrosis

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