Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS)

This study has been completed.
Sponsor:
Collaborators:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier:
NCT00709280
First received: July 1, 2008
Last updated: February 11, 2013
Last verified: February 2013

July 1, 2008
February 11, 2013
April 2009
October 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
The average change in functional residual capacity (FRC) measured by plethysmography during infant pulmonary function testing (iPFT) [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00709280 on ClinicalTrials.gov Archive Site
  • Symptoms by parent home questionnaire administered weekly [ Time Frame: during the 48 week treatment period ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Standardized cough score assessed at study visits [ Time Frame: during the 48 week treatment period ] [ Designated as safety issue: No ]
  • Change in weight, height, resting respiratory rate, and room air oxygen saturation [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • The number of protocol-defined pulmonary exacerbations requiring treatment with oral, inhaled or intravenous antibiotics [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: Yes ]
  • Rates of adverse events, withdrawal, adherence to treatment, new isolation of CF pathogens from respiratory cultures, resting respiratory rate, and room air oxygen saturations [ Time Frame: over the 48 week treatment period ] [ Designated as safety issue: Yes ]
  • The rate of protocol-defined intolerance to the test dose of HS [ Time Frame: at the Screening Visit ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Infant Study of Inhaled Saline in Cystic Fibrosis
Infant Study of Inhaled Saline in Cystic Fibrosis

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cystic Fibrosis
  • 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 Name: Hyper-Sal™, inhaled saline
  • 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 Name: Normal saline
  • Experimental: Active treatment group
    7% Hypertonic Saline administered via inhalation twice daily for 48 ± 4 weeks
    Intervention: Drug: 7% Hypertonic Saline (HS)
  • Active Comparator: Control group
    0.9% Isotonic Saline administered via inhalation twice daily for 48 ± 4 weeks
    Intervention: Drug: 0.9% Isotonic Saline (IS)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
321
November 2011
October 2011   (final data collection date for primary outcome measure)

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
Both
4 Months to 59 Months
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00709280
ISIS002, U01HL092931, U01HL092932
Yes
CF Therapeutics Development Network Coordinating Center
CF Therapeutics Development Network Coordinating Center
  • Cystic Fibrosis Foundation
  • National Heart, Lung, and Blood Institute (NHLBI)
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
CF Therapeutics Development Network Coordinating Center
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP