Magnesium Nebulization Utilization in Management of Pediatric Asthma (MAGNUMPA)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Acute Asthma	Drug: Magnesium Sulfate Sandoz; Drug: Sodium Chloride , USP PPC	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	816 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Magnesium Nebulization Utilization in Management of Pediatric Asthma
Study Start Date :	September 2011
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	December 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Experimental Group; 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.	Drug: Magnesium Sulfate Sandoz; Each treatment will utilize 600 mg (1.2 mL) of Magnesium Sulfate Sandoz; Other Name: Magnesium Sulfate, USP 50% PPC
Placebo Comparator: Control Group; 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.	Drug: Sodium Chloride , USP PPC; Intervention: The control group will receive Sodium Chloride , USP PPC (1.2 mL hypertonic 5.5% saline with 5 mg Salbutamol - GlaxoSmithKline/Pharmascience; Other Name: Sodium Chloride for Injection USP Omega Laboratories Ltd.

Outcome Measures

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Primary Outcome Measures :

1. Hospitalization of Subject [ Time Frame: 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 :

1. Pediatric Respiratory Assessment Measure (PRAM) [ Time Frame: 0, 20, 40 60, 120, 180, 240 minutes post dose ]
2. Changes in Vitals [ Time Frame: 0, 20, 40, 60, 120, 180, 240 minutes post dose ]
   Respiratory Rate, O2 saturation, Blood pressure
3. Number of Salbutamol Treatments [ Time Frame: Up to 240 minutes post dose ]
4. Medical History and Phenotype [ Time Frame: 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

Eligibility Criteria

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Ages Eligible for Study:	2 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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, 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.

Contacts and Locations

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Contacts

Contact: Judy Sweeney, RN	416-813-7838	judy.sweeney@sickkids.ca
Contact: Henna Mian	413-813-7654 ext 202386	henna.mian@sickkids.ca

Locations

Canada, Alberta
Alberta Children's Hospital	Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Jianling Xie Jianling.xie@albertahealthservices.ca
Principal Investigator: Stephen Freedman, MD
Principal Investigator: David Johnson, MD
Stollery Hospital	Recruiting
Edmonton, Alberta, Canada, T6G1C9
Contact: Nadia Dow 7804920451 ndow@ualberta.ca
Principal Investigator: Sarah Curtis, MD
Canada, British Columbia
BC Children's Hospital	Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Jessie Dhillon 604 875-2345 ext 5155 jessie.dhillon@cw.bc.ca
Principal Investigator: Karen Black, MD
Canada, Manitoba
The Manitoba Institute of Child Health	Terminated
Winnipeg, Manitoba, Canada, R3E3P4
Canada, Ontario
Children's Hospital of Eastern Ontario	Recruiting
Ottawa, Ontario, Canada, K1H8L1
Contact: Candice McGahern 6137377600 ext 4111 cmcgahern@cheo.on.ca
Principal Investigator: Roger Zemek, MD
Principal Investigator: Amy Plint, MD
The Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada, M5V1X8
Contact: Judy Sweeney, RN 416-813-7838 judy.sweeney@sickkids.ca
Principal Investigator: Suzanne Schuh, M.D.
Canada, Quebec
Ste Justine Hospital	Recruiting
Montreal, Quebec, Canada, H3T1C5
Contact: Maryse Lagace maryse.legace@recherche-ste-justine.qc.ca
Principal Investigator: Jocelyn Gravel, MD

Sponsors and Collaborators

The Hospital for Sick Children

Canadian Institutes of Health Research (CIHR)

Alberta Children's Hospital

St. Justine's Hospital

Children's Hospital of Eastern Ontario

Stollery Children's Hospital

The Children's Hospital of Winnipeg

Provincial Health Services Authority

Investigators

Principal Investigator:	Suzanne Schuh, MD	The Hospital for Sick Children

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Schuh S, Sweeney J, Freedman SB, Coates AL, Johnson DW, Thompson G, Gravel J, Ducharme FM, Zemek R, Plint AC, Beer D, Klassen T, Curtis S, Black K, Nicksy D, Willan AR; Pediatric Emergency Research Canada Group. Magnesium nebulization utilization in management of pediatric asthma (MagNUM PA) trial: study protocol for a randomized controlled trial. Trials. 2016 May 24;17(1):261. doi: 10.1186/s13063-015-1151-x.

Responsible Party:	Suzanne Schuh, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT01429415 History of Changes
Other Study ID Numbers:	1000024908
First Posted:	September 7, 2011
Last Update Posted:	November 24, 2017
Last Verified:	November 2017

Keywords provided by Suzanne Schuh, The Hospital for Sick Children:

pediatric; Acute Asthma; Inhaled Magnesium

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Magnesium Sulfate; Analgesics; Sensory System Agents	Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Anti-Arrhythmia Agents; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Tocolytic Agents; Reproductive Control Agents