Hypertonic Saline as Add on Therapy in Preschool Children With Acute Wheezing Attack.

• ClinicalTrials.gov Identifier: NCT01073527
• Recruitment Status: Completed
• First Posted: February 23, 2010
• Last Update Posted: August 9, 2011
• Sponsor: Wolfson Medical Center
• Information provided by: Wolfson Medical Center

Study Description

Brief Summary:

To investigate the efficacy of adding Inhaled Hypertonic Saline treatment (HS) for 1-6 year old children with "asthmatic" attack presenting to Emergency Department (ED).

Background: In 1-6 year old children, the most common causes of acute exacerbations of asthma requiring urgent medical care are viral respiratory infections. Most of these children are not atopic and often do not respond very well to bronchodilators and steroids. Thus novel treatments are needed.

HS is considered an effective and safe treatment for infants with acute viral bronchiolitis (Cochrane 2008). HS acts in the airways in several mechanisms: HS re-hydrates secretions and improving mucus rheology, reduce edema of the airway wall by absorbing water from the mucosa and submucosa, causes sputum induction and cough, which can help to clear the sputum out of the bronchi, stimulates cilial beat via the release of prostaglandin E2, breaks the ionic bonds within the mucus gel, thereby lowering the viscosity and elasticity of the mucus secretion.

It is estimated that all the above HS responding elements may play a role in this viral induce wheezing. The above mentioned theoretical benefits provide the rationale for the possible treatment of viral induced acute wheezing ("asthma") attack with nebulized HS in young pre-school children presenting to the Pediatric Emergency Unit with acute (mostly viral induced) wheezing.

Therefore, the purpose of the present study is to 1. Investigate the addition of frequently nebulized 5% HS/albuterol combination to standard therapy of acute asthmatic episodes presenting to the emergency department (ED) in preschool children in a prospective, randomized, double-blind, controlled fashion.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: hypertonic saline-salbutamol combination; Drug: Normal saline-salbutamol combination	Not Applicable

Detailed Description:

A randomized double blind, controlled, (DBCR) trial. To investigate the efficacy of adding inhaled Hypertonic Saline (HS) treatment for 1-6 year old children with asthmatic attack presenting to ED

Background:

Children under the age of 5 years have the highest hospitalization rate of asthma. The most common causes of acute exacerbations of asthma requiring urgent medical care are viral respiratory infections. Most of these children < 6 years old are not atopic.

These investigators have previously demonstrated in wheezy infants with acute viral bronchiolitis that nebulized hypertonic saline produces a clinical significant reduction in length of hospital stay and improves the clinical score and is considered an effective and safe treatment for infants with acute viral bronchiolitis (Cochrane 2008).

Hypertonic saline solution acts in the airways in several mechanisms:

It Stimulates ciliar beat via the release of prostaglandin E2 and increases mucociliary clearance.

It Breaks the ionic bonds within the mucus gel, thereby reducing the degree of cross linking and entanglements and lowering the viscosity and elasticity of the mucus secretion.

HS induces an osmotic flow of water into the mucus layer, re-hydrating secretions and improving mucus rheology.

HS reduces edema of the airway wall by absorbing water from the mucosa and submucosa.

HS can cause sputum induction and cough, which can help to clear the sputum outside of the bronchi and thus improve airway obstruction.

It is estimated that many of the above hypertonic saline responding elements may play a role in this viral induce wheezing such as: mucosal and submucosal edema, peribronchial infiltrate of inflammatory cells, necrosis and desquamation of ciliated epithelial cells, and excess mucus secretion. The combination of an airway wall swelling, sloughing of necrotic debris, increased mucus production and impaired secretion clearance, eventually contribute in addition to bronchospasm to airway obstruction, gas trapping, atelectasis and impaired gas exchange. Moreover, as postulated in "status asthmatic", the relative contribution of these "non-spasmodic" pathological and pathophysiological consequences of viral and asthmatic inflammation to airway obstruction, gas trapping, atelectasis and impaired gas exchange become even more important in these children already treated with maximum dilatation dose of bronchodilating drugs in the emergency department.

The above mentioned theoretical benefits provide the rationale for the possible treatment of viral induced acute wheezing ("asthma") attack with nebulized hypertonic saline solution in young pre-school children presenting to the Pediatric Emergency Unit with acute (mostly viral induced) wheezing.

Therefore, the purpose of the present study is to investigate the addition of frequently nebulized 5% HS/albuterol combination to standard therapy of acute asthmatic episodes presenting to the ED in preschool children in a prospective, randomized, double-blind, controlled fashion.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Interventional Study: Hypertonic Saline as Add on Treatment to the Usual Therapy for Preschool Children With Acute "Asthmatic" Attack Presenting to the ER: A Double Blind Control Study
• Study Start Date: January 2009
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Hypertonic saline-salbutamol combination; NaCl 5% - 4cc (with standard treatment - salbutamol 0.5cc)	Drug: hypertonic saline-salbutamol combination; hypertonic saline 5% with 0.5cc salbutamol; Other Name: Preschool asthma,Induced sputum, Metacholine,Adenosine
Placebo Comparator: normal saline-salbutamol combination; Standard treatment normal saline 4cc with salbutamol 0.5cc	Drug: Normal saline-salbutamol combination; normal saline - 4cc with salbutamol 0.5cc; Other Name: Preschool asthma

Outcome Measures

Primary Outcome Measures :

1. shortening length of stay (LOS) [ Time Frame: From admision to ready to discharge. ]

Secondary Outcome Measures :

1. Hospitalization rate [ Time Frame: From presenting to ED until admission to hospital ]
2. Improvement in clinical score (CS) [ Time Frame: Post inhalations on presentation to the ED and daily during hospitalization ]

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Children, age: 1-6 years old
• Presenting to the ED with acute wheezing episode

Exclusion Criteria:

• Any chronic (lung, cardiac, immunologic, neurologic) disease

Contacts and Locations

Locations

Israel

The Edith Wolfson MC

Holon, Israel

Sponsors and Collaborators

Wolfson Medical Center

Investigators

• Principal Investigator: Avigdor Mandelberg, MD; The Sackler School of Medicine, Tel Aviv University, Israel

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ater D, Shai H, Bar BE, Fireman N, Tasher D, Dalal I, Ballin A, Mandelberg A. Hypertonic saline and acute wheezing in preschool children. Pediatrics. 2012 Jun;129(6):e1397-403. doi: 10.1542/peds.2011-3376. Epub 2012 May 21.

• Responsible Party: Avigdor Mandelberg MD, Director, Pediatric Pulmonary Unit, Wolfson Medical Center, Holon, Israel, The Sackler School of Medicine, Tel Aviv University
• ClinicalTrials.gov Identifier: NCT01073527 History of Changes
• Other Study ID Numbers: 1038
• First Posted: February 23, 2010
• Last Update Posted: August 9, 2011
• Last Verified: August 2011

Keywords provided by Wolfson Medical Center:

Child, preschool; Pediatric emergency department

Additional relevant MeSH terms:

Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action