ISIS: Infant Study of Inhaled Saline in Cystic Fibrosis

Sponsor

CF Therapeutics Development Network Coordinating Center (Other)

Overall Status

Completed

CT.gov ID

NCT00709280

Collaborator

Cystic Fibrosis Foundation (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

321

Enrollment

Locations

Arms

Duration (Months)

10.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: 7% Hypertonic Saline (HS) Drug: 0.9% Isotonic Saline (IS)	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

321 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Infant Study of Inhaled Saline in Cystic Fibrosis

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active treatment group 7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks	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. Other Names: Hyper-Sal™, inhaled saline
Active Comparator: Control group 0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks	Drug: 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. Other Names: Normal saline

Arm

Intervention/Treatment

Experimental: Active treatment group

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

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.

Other Names:

Hyper-Sal™, inhaled saline

Active Comparator: Control group

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

Drug: 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.

Other Names:

Normal saline

Outcome Measures

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 [during the 48 week treatment period]

Secondary Outcome Measures

Symptoms by parent home questionnaire administered weekly [during the 48 week treatment period]
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]
Standardized cough score assessed at study visits [during the 48 week treatment period]
Change in weight, height, resting respiratory rate, and room air oxygen saturation [over the 48 week treatment period]
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Months to 59 Months

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Stanford University / Lucile S. Packard Children's Hospital	Palo Alto	California	United States	94304
4	The Children's Hospital	Aurora	Colorado	United States	80045
5	Children's Memorial Hospital and Northwestern University	Chicago	Illinois	United States	60614
6	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
7	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
8	University of Louisville	Louisville	Kentucky	United States	40202
9	Johns Hopkins University / Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
10	University of Michigan / C.S. Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
11	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
12	Cardinal Glennon Children's Hospital	St. Louis	Missouri	United States	63104
13	Washington University in St. Louis	St. Louis	Missouri	United States	63110
14	University of Nebraska	Omaha	Nebraska	United States	68198
15	Women and Children's Hospital of Buffalo	Buffalo	New York	United States	14222
16	University of Rochester Medical Center	Rochester	New York	United States	14642
17	SUNY Upstate Medical University	Syracuse	New York	United States	13210
18	University of North Carolina	Chapel Hill	North Carolina	United States	27599
19	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
20	Nationwide Children's Hospital, Pulmonary Division	Columbus	Ohio	United States	43205
21	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
22	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15201
23	Texas Children's Hospital	Houston	Texas	United States	77030
24	University of Utah	Salt Lake City	Utah	United States	84108
25	University of Virginia - Pediatric Respiratory Medicine	Charlottesville	Virginia	United States	22908
26	Children's Hospital & Regional Medical Center	Seattle	Washington	United States	98105
27	University of Wisconsin	Madison	Wisconsin	United States	53792
28	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
29	BC Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
30	Hospital For Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

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

Investigators

Principal Investigator: Stephanie Davis, MD, University of North Carolina, Chapel Hill
Principal Investigator: Margaret Rosenfeld, MD, MPH, Children's Hospital and Regional Medical Center
Principal Investigator: Felix Ratjen, MD, PhD, University of Toronto Hospital for Sick Children