Magnesium Nebulization Utilization in Management of Pediatric Asthma

Phase 2

Completed

• Conditions: Acute Asthma
• Interventions: Drug: Magnesium Sulfate Sandoz; Drug: Sodium Chloride , USP PPC

• Registration Number: NCT01429415
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

Acute asthma is the most common cause of pediatric hospitalizations. While the investigators know that repeat inhalations of ß2 agonists and ipratropium with early oral steroids substantially reduce hospitalizations, many children are resistant to this standard initial therapy. About a third of children remaining in moderate to severe distress after standard therapy are admitted to hospital and comprise 84% of pediatric acute asthma hospitalizations. Finding safe, non-invasive, and effective strategies to treat children resistant to standard therapy would substantially decrease hospitalizations resulting in considerable health care savings and reduction of the psycho-social burden of the disease. While studies of magnesium sulfate (Mg) given intravenously (IV) suggest that this agent can reduce hospitalizations in both adults and children resistant to standard initial therapy Nebulization is an alternate route for administering Mg. This route has the advantage of being non-invasive and is likely much safer due to lower systemic delivery. Direct delivery via nebulization allows higher Mg concentrations at the target site, the lower airways, with a smaller total drug dose. The investigators propose to conduct a properly designed study to clarify the role of nebulized Mg.

Detailed Description

The investigators plan the following specific aims:

1. Primary Objective: To examine if in children with acute asthma remaining in moderate to severe respiratory distress despite maximized initial bronchodilator and steroid therapy there is a reduction in hospitalization rate from the ED in those who receive nebulized Mg with salbutamol versus those receiving salbutamol only.

Hypothesis: The investigators hypothesize that the children with Pediatric Respiratory Assessment Measure (PRAM) ≥ 5 points after optimized initial inhaled bronchodilator and oral steroid therapies who are given nebulized Mg in addition to nebulized salbutamol will have significantly lower hospitalization rate within 24 hours of starting the study compared to those given salbutamol only.

2. To compare a difference in the changes in the validated Pediatric Respiratory Assessment Measure (PRAM), respiratory rate, oxygen saturation and blood pressure from randomization baseline to 240 minutes in the two groups

3. To determine if there is a significant association between the difference in the primary outcome between the groups and the patient's age, gender, baseline PRAM score, personal history of atopy and "viral-induced wheeze" phenotype.

Hypothesis(es) to be Tested In this randomized, double-blind seven-centre trial, the investigators hypothesize that children with acute asthma with a Pediatric Respiratory Assessment Measure (PRAM) of ≥ 5 points after optimized initial inhaled bronchodilator and oral steroid therapies who are given nebulized Mg in addition to nebulized salbutamol will have at least a 10% lower hospitalization rate within 24 hours of starting the study as compared to those given salbutamol only.

Study Timeline

• Study First Submitted: 2011-09-02
• Study First Submitted QC: 2011-09-06
• Study First Posted: 2011-09-07
• Study Start: 2011-09-26
• Primary Completion: 2019-11-19
• Study Completion: 2019-11-22
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-31
• Last Update Posted: 2020-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 818

Inclusion Criteria

1. 2-17 years of age
2. Diagnosis of asthma/reactive airways/viral wheeze, defined as this diagnosis made by a physician and at least one prior acute episode of wheezing with cough or dyspnea treated with inhaled ß2 agonists or oral corticosteroids. Our study population will exclude bronchiolitis and first-time wheeze (potential alternate diagnoses).
3. Persistent moderate to severe airway obstruction after 3 doses of salbutamol and ipratropium (as per site specific standard of care guidelines) -, defined as a PRAM 5 or higher. A PRAM score of 5 or more following initial therapy indicates the child has at least moderate disease severity and has a high likelihood of being hospitalized.This group of children includes 84% of all pediatric asthma hospitalizations; therefore, finding an effective therapy for this population has great potential to significantly reduce hospitalizations. (Appendix B).

Exclusion Criteria

1. No previous history of wheezing or bronchodilator therapy. Some children who present with wheezing for the first time will have other diagnoses which would not be expected to respond to Mg.
2. Patients who have already received IV Mg therapy during the index visit.
3. Critically ill children requiring immediate intubation. These children need immediate ICU management and hospitalization.
4. Children who in the opinion of the treating physician require a chest radiograph due to atypical clinical presentation and are found to have radiologist-confirmed pneumonia. These rare patients may have to be hospitalized primarily for treatment of the infection and may not respond to magnesium.
5. Known co-existent renal, chronic pulmonary, neurologic, cardiac or systemic disease. These conditions may influence the response to Mg and hospitalization.
6. Known hypersensitivity to Mg sulfate.
7. Patients previously enrolled in the study.
8. Insufficient command of the English and or French language.
9. Lack of a home or cellular telephone.
10. Known allergy/sensitivity to latex.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Group	Magnesium Sulfate Sandoz	Magnesium Sulfate Sandoz/PPC 600mg and Salbutamol (GlaxoSmithKline/Pharmascience) 5mg by inhalation via Aeroneb Go nebulizer (Philips) with Idehaler Pocket chamber DTF q 20 minutes, 3 treatments.
Control Group	Sodium Chloride , USP PPC	Sodium Chloride USP PPC/Omega (5.5%) placebo and salbutamol GlaxoSmithKline/Pharmascience 5 mg by inhalation via Aeroneb Go nebulizer Philips with Idehaler Pocket chamber DTF q 20 minutes, 3 treatments.

Primary Outcome Measures

Name	Time	Method
Hospitalization of Subject	Up to 24 hours after treatment	Defined as admission to an inpatient unit within 24hours of the start of experimental therapy due to continued/worsening distress.

Secondary Outcome Measures

Name	Time	Method
Medical History and Phenotype	Baseline	The investigators will measure hospitalization and age, gender, pre-randomization PRAM score, personal history of atopy, and "acute viral induced wheeze" phenotype. This phenotype will be defined by age less than 5 years, co-existent upper respiratory tract infection, no interval symptoms between exacerbations, no atopy
Number of Salbutamol Treatments	Up to 240 minutes post dose	This measure of additional therapy may strengthen the measure of benefit of inhaled magnesium
Pediatric Respiratory Assessment Measure (PRAM)	0, 20, 40 60, 120, 180, 240 minutes post dose	PRAM is a validated measure of asthma severity in the Emergency Department
Changes in Vitals	0, 20, 40, 60, 120, 180, 240 minutes post dose	Respiratory Rate, O2 saturation, Blood pressure

Trial Locations

Locations (7)

Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Ste Justine Hospital; 🇨🇦 Montreal, Quebec, Canada

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

The Manitoba Institute of Child Health; 🇨🇦 Winnipeg, Manitoba, Canada

Stollery Hospital; 🇨🇦 Edmonton, Alberta, Canada

BC Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada