Infant Study of Inhaled Saline in Cystic Fibrosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Infant Study of Inhaled Saline in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: 7% Hypertonic Saline (HS)
* Drug: 0.9% Isotonic Saline (IS)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment group<br>7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks | Drug: 7% Hypertonic Saline (HS)<br>* 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.<br>* Other names: Hyper-Sal™, inhaled saline;|
| Active Comparator: Control group<br>0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks | Drug: 0.9% Isotonic Saline (IS)<br>* 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.<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, hypertonic saline, inhaled saline