Clinical trial NCT01247064: Hypertonic Saline for Acute Bronchiolitis
Official title: Nebulized Hypertonic Saline for Acute Bronchiolitis in the Emergency Department
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bronchiolitis, Viral
Saline Solution, Hypertonic
Keywords: Bronchiolitis
Hypertonic Saline
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2010-11-24
Enrollment: 62
Sex: ALL
Minimum age (years): 2
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether nebulized 3% hypertonic saline (HS) improves respiratory distress in children 2-23 months presenting to the emergency department (ED) with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.

Detailed description: Acute bronchiolitis is the most frequent cause of infant hospitalization in the United States. Bronchiolitis typically refers to a viral lower respiratory tract infection during the first two years of life manifesting as a constellation of clinical symptoms including wheezing, cough and respiratory distress. In addition to a tremendous disease burden, bronchiolitis admissions in the United States cost more than $500 million each year.

The primary pathophysiologic processes in bronchiolitis include airway wall and peribronchial inflammation, increased mucous production, sloughing of necrotic epithelial cells, and impaired airway clearance. These processes result in airway obstruction, gas trapping, atelectasis and impaired gas exchange. Standard therapies for bronchiolitis remain supportive, including maintaining hydration and nutrition, ensuring adequate oxygenation, and physical suctioning of the nasal airways to clear secretions. Therapies such as the bronchodilator albuterol, although commonly used in standard practice, have not been proven to impact progression of disease or improve long-term outcomes of bronchiolitis.

Nebulized hypertonic saline (HS) has been shown to increase mucociliary clearance in the airways of individuals with healthy lungs. In addition nebulized HS increases airway clearance for disease processes including asthma, cystic fibrosis and bronchiectasis. A recent Cochrane review examined 4 small studies that suggest that nebulized 3% HS may reduce length of hospital stay and improve clinical severity scores in infants with acute viral bronchiolitis. None of these studies have explored the use of nebulized HS in the emergency department (ED). A recent study examined the use of a single nebulized treatment of epinephrine mixed in 3% HS in 46 infants less than 12 months presenting to the ED with bronchiolitis. This study did not find a difference between epinephrine diluted in normal saline compared to epinephrine diluted in 3% HS. Despite no effect on clinical score, the investigators did note a trend toward decreased rates of hospitalization. Furthermore, since this was the first ED study and the first negative study, the authors concluded that further investigation is necessary to determine if HS has a role in the management of acute bronchiolitis.

The purpose of the current study is to determine whether nebulized 3% HS improves respiratory distress in children 2-23 months presenting to the ED with acute bronchiolitis with persistent respiratory distress after initial therapy with a trial of nebulized albuterol.

Given the tremendous clinical and financial burden of bronchiolitis, any effective therapy, particularly one that is inexpensive, has the potential to result in significant health care savings. If nebulized 3% HS improved clinical scores in the ED, this may provide an inexpensive, safe and effective therapy for children with bronchiolitis in the acute care setting.

Eligibility criteria: Inclusion Criteria:

* Age 8 weeks through 23 months
* First episode of wheezing associated with respiratory distress and upper respiratory tract infection.
* Respiratory Distress Assessment Instrument (RDAI) rating of ≥4 and ≤15 after initial albuterol nebulization per standard care
* Pediatric Emergency Medicine (PEM) physician does not plan additional bronchodilator therapy within the hour after initial assessment.
* Parental/guardian permission (informed consent)

Exclusion Criteria:

* Subjects with prior history of wheezing or asthma or who have received bronchodilator therapy prior to the current illness
* Chronic lung or heart disease
* Critically ill infants requiring immediate airway stabilization
* Non-English speaking parent/guardian
* Inability to take nebulized medications

Primary outcomes:
measure: Respiratory Assessment Change Score (RACS)
timeFrame: Baseline and 1 hour
Secondary outcomes:
measure: Rate of Hospitalization
timeFrame: 1 day
measure: Respiratory Rate Change
timeFrame: Baseline and 1 hour
measure: Oxygen Saturation Change
timeFrame: Baseline and 1 hour
measure: Parental Perception of Improvement of Breathing After Study Medication
timeFrame: 1 hour
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Joseph Zorc, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Todd Florin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grewal S, Ali S, McConnell DW, Vandermeer B, Klassen TP. A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department. Arch Pediatr Adolesc Med. 2009 Nov;163(11):1007-12. doi: 10.1001/archpediatrics.2009.196.
citation: Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006458. doi: 10.1002/14651858.CD006458.pub2.
citation: Kuzik BA, Al-Qadhi SA, Kent S, Flavin MP, Hopman W, Hotte S, Gander S. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr. 2007 Sep;151(3):266-70, 270.e1. doi: 10.1016/j.jpeds.2007.04.010. Epub 2007 Jun 29.
citation: Tal G, Cesar K, Oron A, Houri S, Ballin A, Mandelberg A. Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience. Isr Med Assoc J. 2006 Mar;8(3):169-73.
citation: Mandelberg A, Tal G, Witzling M, Someck E, Houri S, Balin A, Priel IE. Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis. Chest. 2003 Feb;123(2):481-7. doi: 10.1378/chest.123.2.481.
citation: Sarrell EM, Tal G, Witzling M, Someck E, Houri S, Cohen HA, Mandelberg A. Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms. Chest. 2002 Dec;122(6):2015-20. doi: 10.1378/chest.122.6.2015.
citation: Florin TA, Shaw KN, Kittick M, Yakscoe S, Zorc JJ. Nebulized hypertonic saline for bronchiolitis in the emergency department: a randomized clinical trial. JAMA Pediatr. 2014 Jul;168(7):664-70. doi: 10.1001/jamapediatrics.2013.5306.