title: Magnesium nebulization utilization in management of pediatric asthma (MagNUM PA) trial: study protocol for a randomized controlled trial.
abstract: Up to 30 % of children with acute asthma are refractory to initial therapy, and 84 % of this subpopulation needs hospitalization. Finding safe, noninvasive, and effective strategies to treat this high-risk group would substantially decrease hospitalizations, healthcare costs, and the psycho-social burden of the disease. Whereas intravenous magnesium (Mg) is effective in severe refractory asthma, its use is sporadic due to safety concerns, with the main treatment goal being to prevent intensive care unit admission. In contrast, nebulized Mg is noninvasive, allows higher pulmonary drug concentrations, and has a much higher safety potential due to the lower rate of systemic delivery. Previous studies of inhaled Mg show disparate results due to the use of unknown/inefficient delivery methods and other methodological flaws.
  
  
  
  The study is a randomized double-blind controlled trial in seven Canadian pediatric Emergency Departments (two-center pilot 2011 to 2014, Canada-wide November 2014 to December 2017). The trial will include 816 otherwise healthy children who are 2 to 17 years old, having had at least one previous wheezing episode, have received systemic corticosteroids, and have a Pediatric Respiratory Assessment Measure (PRAM) ≥ 5 points after three salbutamol and ipratropium treatments for a current acute asthma exacerbation. Eligible consenting children will receive three experimental treatments of nebulized salbutamol with either 600 mg of Mg sulfate or placebo 20 min apart, using an Aeroneb Go nebulizer, which has been shown to maximize pulmonary delivery while maintaining safety. The primary outcome is hospitalization within 24 h of the start of the experimental therapy for persistent respiratory distress or supplemental oxygen. Secondary outcomes include all-cause hospitalization within 24 h, PRAM, vital signs, number of bronchodilator treatments by 240 min, and the association between the difference in the primary outcome between the groups, age, gender, baseline PRAM, atopy, and "viral induced wheeze" phenotype (Fig. 1).
  
  
  
  If effective, inhaled Mg may represent an effective strategy to minimize morbidity in pediatric refractory acute asthma. Unlike previous works, this trial targets nonresponders to optimized initial therapy who are the most likely to benefit from inhaled Mg. Future dissemination of results will include knowledge translation, incorporation into a Cochrane Review, presentation at scientific meetings, and a peer-reviewed publication.
  
  
  
  NCTO1429415 , registered 2 September 2011.
authors.affiliation: Division of Paediatric Emergency Medicine, The Hospital for Sick Children, Child Health Evaluative Sciences, SickKids Research Institute, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. Suzanne.schuh@sickkids.ca.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Schuh
authors.affiliation: SickKids Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: Sweeney
authors.affiliation: Sections of Pediatric Emergency Medicine and Gastroenterology, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6AB, Canada.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Freedman
authors.affiliation: SickKids Research Institute, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Allan L
authors.initials: AL
authors.lastname: Coates
authors.affiliation: Departments of Paediatrics, Pharmacology and Physiology, Alberta Children's Hospital Research Institute, Faculty of Medicine, University of Calgary, C4,643, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6AB, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Division of Pediatric Emergency Medicine, Alberta Children's Hospital, University of Calgary, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6AB, Canada.
authors.forename: Graham
authors.initials: G
authors.lastname: Thompson
authors.affiliation: Division of Paediatric Emergency Medicine, Department of Pediatrics, Centre Hospitalier Universitaire Ste-Justine, Université de Montréal, 3175 Cote Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Gravel
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire Ste-Justine, Université de Montréal, 175 Cote Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.
authors.forename: Francine M
authors.initials: FM
authors.lastname: Ducharme
authors.affiliation: Division of Pediatric Emergency Medicine, Children's Hospital of Eastern Ontario (CHEO), 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
authors.forename: Roger
authors.initials: R
authors.lastname: Zemek
authors.affiliation: Division of Emergency Medicine, Children's Hospital of Eastern Ontario (CHEO), 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Plint
authors.affiliation: Divsion of Pediatric Emergency Medicine, The Children's Hospital of Winnipeg, University of Manitoba, 820 Sherbrook Street, Winnipeg, MB, R3J 1R9, Canada.
authors.forename: Darcy
authors.initials: D
authors.lastname: Beer
authors.affiliation: Children's Hospital Research Institute of Manitoba (formerly Manitoba Institute of Child Health), Academic Faculty of Medicine, 715 McDermot Ave, Winnipeg, MB, R3E 3P4, Canada.|Department of Pediatrics and Child Health, University of Manitoba, 715 McDermot Ave, Winnipeg, MB, R3E 3P4, Canada.|Child Health Program, Winnipeg Health Region MICH, 715 McDermot Ave, Winnipeg, MB, R3E 3P4, Canada.
authors.forename: Terry
authors.initials: T
authors.lastname: Klassen
authors.affiliation: Division of Paediatric Emergency Medicine, Stollery Children's Hospital, University of Alberta, 8440 112 Street Northwest, Edmonton, AB, T6G 2B7, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Curtis
authors.affiliation: Division of Pediatric Emergency Medicine, University of British Columbia, BC Children's Hospital, 4480 Oak St, Vancouver, BC, V6H 3N1, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Black
authors.affiliation: SickKids Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
authors.forename: Darcy
authors.initials: D
authors.lastname: Nicksy
authors.affiliation: Child Health Evaluative Sciences, SickKids Research Institute, Dalla Lana School of Public Health, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Willan
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D004311:Double-Blind Method; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage* / Q000009:adverse effects; D017063:Outcome Assessment, Health Care
chemical_list: D008274:Magnesium
keywords: Randomized controlled trial; acute asthma; children; magnesium