Clinical trial NCT06785272: Magnesium Trial in Acute Asthma in Emergency Department
Official title: Magnesium Trial in Acute Asthma in Emergency Department
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Asthma
Keywords: asthma, magnesium sulfate
pediatric, acute asthma
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Alberta Children's Hospital
name: McMaster Children's Hospital
name: Stollery Children's Hospital
name: Children's Hospital of Eastern Ontario
name: St. Justine's Hospital
First posted: 2025-01-21
Enrollment: 192
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite optimal initial emergency department (ED) therapy, 50% of children with severe acute asthma have ongoing moderate-severe respiratory distress. Guidelines recommend intravenous magnesium (IVMg) for them, yet evidence for IVMg efficacy is scant and disparate. While early small Randomized Controlled Trials (RCTs) suggested hospitalization benefit, recent large observational studies found no association between IVMg and improved outcomes. IVMg therapy is resource-intensive, can cause hypotension and demands close monitoring. Previous RCTs only assessed early Mg effect at 1-2 hours, overlooked the peak effect of key co-interventions such as corticosteroids and did not use validated scores. IVMg use is variable and often delayed until ≥4 hours after ED therapy is started and after the hospitalization decision has been made. Thus, in observational studies children given IVMg are 6-10 times more likely to be hospitalized; these studies have major confounding and the true IVMg treatment effect is thus unknown. To conclusively determine if IVMg alters the exacerbation course, it must be given early, and the primary outcome measure should be the severity of respiratory distress measured at the peak effect of key co-interventions to focus on a clinically meaningful and objective effect. The Pediatric Respiratory Assessment Measure (PRAM)-a valid, discriminative, reproducible and responsive-to-change instrument-is thus the ideal primary outcome measure. Hospitalization outcome has major confounding by indication and MD perceptions.

Primary Aim: In children with acute asthma remaining in moderate-severe distress after 1 hour of initial ED therapy, is early IVMg therapy associated with a significantly greater improvement in respiratory distress, measured by PRAM, at 3 hours after starting the intervention, compared to placebo? Hypothesis: IVMg will yield significantly greater PRAM improvement of ≥1.0 point than placebo.

Expected Outcomes: This trial will clarify if there is an incremental benefit of IVMg in decreasing respiratory distress in pediatric refractory acute asthma. A positive result will establish a proven standard of care for this indication, with a need for Knowledge Translation (KT) to implement routine early IVMg therapy. A negative result will lead to de-implementation of IVMg which may also lead to cost savings.

Detailed description: The investigators propose a 6-centre randomized, double-blind, placebo-controlled trial. Two groups will be compared: IVMg sulfate and IV (intravenous) 0.9% saline placebo. After initial therapy with the systemic Corticosteroids (CSs) routinely used for acute asthma management at a given site, 3 treatments with inhaled salbutamol and ipratropium, eligible patients with PRAM ≥5 will, under the care of the research nurse, receive a 30-minute IV infusion of 75 mg/kg of Mg sulfate (maximum 2.0 g) \[experimental group\] or an identical volume of 0.9% saline \[control group\]. Outcomes will be measured during the 180-minute observational period in the ED and at 72 hours post ED discharge.

Eligibility criteria: Inclusion criteria:

1. Age 2-17 years,
2. Diagnosis of asthma, defined as an asthma diagnosis/asthma phenotype made by a physician (this includes ED physician) and at least one prior episode of asthma-like symptoms responsive to inhaled ß2 agonists or oral/inhaled CSs.
3. Moderate-severe asthma after initial therapy with 3 treatments of inhaled salbutamol and ipratropium, defined as a PRAM ≥5, indicating a strong association with hospitalization.

Exclusion criteria:

1. No past history of wheeze/bronchodilator therapy. Some children with the first wheeze may have other diagnoses not responsive to Mg.
2. Receipt of IVMg within 24 hours prior to ED arrival.
3. Need for airway support on arrival.
4. Known renal, chronic pulmonary, neurologic, cardiac or systemic disease: these may influence outcomes after Mg.
5. Known hypersensitivity to Mg sulfate.
6. Previous enrollment.
7. Poor mastery of English and/or French language precluding informed consent understanding.
8. No phone/email.
9. Known pregnancy.

Primary outcomes:
measure: Pediatric Respiratory Assessment Measure (PRAM) score
timeFrame: The primary outcome measure will be the PRAM score, measured at 30, 60, 120 and 180 minutes post intervention, with the 180 minute measurement as the primary end-point.
Secondary outcomes:
measure: Hospitalization for asthma at the index ED visit
timeFrame: Up to 24 hours after starting experimental therapy
measure: Changes in respiratory rate
timeFrame: From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention (respiratory rate )
measure: Changes in oxygen saturation
timeFrame: From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention ( oxygen saturation)
measure: Changes in blood pressure
timeFrame: From baseline (pre-intervention) to 10,20,30,60,120, and 180 minutes post intervention (blood pressure).
measure: PRAM denoting mild asthma (≤ 3 points is a widely accepted discharge criterion)
timeFrame: at 180 minutes post intervention
measure: Hospitalization for asthma at any medical facility
timeFrame: within 72 hours post- ED discharge
measure: Unscheduled asthma-related visits to any health care provider
timeFrame: within 72 hours post- ED discharge
measure: Hospital length of stay.
timeFrame: From presentation at the Emergency Department triage to the time of hospital discharge, up to 4 weeks.
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Ontario
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montreal
country: Canada
facility: CHU-Sainte Justine Hospital
state: Quebec
Study officials:
affiliation: The Hospital for Sick Children
name: Suzanne Schuh, MD
role: PRINCIPAL_INVESTIGATOR
References: