Infant Study of Inhaled Saline in Cystic Fibrosis

NCT ID: NCT00709280

Last Updated: 2013-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 321 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2011-11-30

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active treatment group

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

Group Type: EXPERIMENTAL

7% Hypertonic Saline (HS)

Intervention Type: DRUG

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.

Control group

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

Group Type: ACTIVE_COMPARATOR

0.9% Isotonic Saline (IS)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Hyper-Sal™, inhaled saline; Normal saline

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

• 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

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

CF Therapeutics Development Network Coordinating Center

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie Davis, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Margaret Rosenfeld, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital and Regional Medical Center

Felix Ratjen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto Hospital for Sick Children

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

Stanford University / Lucile S. Packard Children's Hospital

Palo Alto, California, United States

The Children's Hospital

Aurora, Colorado, United States

Children's Memorial Hospital and Northwestern University

Chicago, Illinois, 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

Johns Hopkins University / Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Michigan / C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Washington University in St. Louis

St Louis, Missouri, United States

University of Nebraska

Omaha, Nebraska, United States

Women and Children's Hospital of Buffalo

Buffalo, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital, Pulmonary Division

Columbus, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Texas Children's Hospital

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Virginia - Pediatric Respiratory Medicine

Charlottesville, Virginia, United States

Children's Hospital & Regional Medical Center

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

BC Children's Hospital

Vancouver, British Columbia, Canada

Hospital For Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 22610452 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23742699 (View on PubMed)

Other Identifiers

U01HL092931

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL092932

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ISIS002

Identifier Type: -

Identifier Source: org_study_id