Magnesium Trial in Acute Asthma in Emergency Department

Phase 3

Not yet recruiting

• Conditions: Asthma
• Interventions: Drug: magnesium sulfate; Drug: Normal Saline

• Registration Number: NCT06785272
• Lead Sponsor: The Hospital for Sick Children

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.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-09
• Study First Submitted QC: 2025-01-17
• Last Update Submitted: 2025-01-17
• Study First Posted: 2025-01-21
• Last Update Posted: 2025-01-21
• Study Start: 2025-09
• Primary Completion: 2027-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 192

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Group	magnesium sulfate	This group will receive a single dose of intravenous magnesium sulfate over 30 minutes. After this treatment has been completed, they may also get further Ventolin inhalations or other asthma medicines which are not part of the study, as recommended by the emergency physician. The participant will be monitored closely by the study nurse who will measure their breathing, heart rate, blood pressure and oxygen for 3 hours after the study treatment. The study nurse will also notify the emergency physician of any major changes.
Placebo Group	Normal Saline	This group, will receive a single dose of intravenous placebo (normal saline, i.e. salt water) over 30 minutes. After this treatment has been completed, they may also get further Ventolin inhalations or other asthma medicines which are not part of the study, as recommended by the emergency physician who is taking care of the participant. They will be monitored closely by the study nurse who will measure the participant's breathing, heart rate, blood pressure and oxygen for 3 hours after the study treatment. The study nurse will also notify the emergency physician of any major changes in their health.

Primary Outcome Measures

Name	Time	Method
Pediatric Respiratory Assessment Measure (PRAM) score	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.	PRAM is a validated 12-point asthma severity score which exhibits the most comprehensive measurement properties of all asthma scores and has been successfully used as an outcome in major trials. It is the only score with demonstrated criterion validity, using respiratory resistance as the gold standard. PRAM has been validated in both preschool and school-aged children in the ED with asthma and has strong association with admission. PRAM has inter-rater reliability above 70% and is adopted in all pediatric EDs in Canada. Most children treated for acute asthma are preschoolers who lack coordination to perform pulmonary function tests reliably. To maximize the accuracy of the PRAM measurement, all study nurses will complete an online PRAM training module. We will use an eligibility cut-off of PRAM ≥ 5 post initial therapy as this is associated with clinically concerning respiratory distress requiring further intervention

Secondary Outcome Measures

Name	Time	Method
Hospitalization for asthma at the index ED visit	Up to 24 hours after starting experimental therapy	Defined as admission to an inpatient unit due to continued/worsening distress
Changes in respiratory rate	From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention (respiratory rate )	Changes in vital signs
Changes in oxygen saturation	From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention ( oxygen saturation)	Changes in vital signs
Changes in blood pressure	From baseline (pre-intervention) to 10,20,30,60,120, and 180 minutes post intervention (blood pressure).	Changes in vital signs
PRAM denoting mild asthma (≤ 3 points is a widely accepted discharge criterion)	at 180 minutes post intervention	PRAM is a validated measure of asthma
Hospitalization for asthma at any medical facility	within 72 hours post- ED discharge	Defined as admission to an inpatient unit due to continued/worsening distress
Unscheduled asthma-related visits to any health care provider	within 72 hours post- ED discharge	Family-initiated asthma-related medical visit
Hospital length of stay.	From presentation at the Emergency Department triage to the time of hospital discharge, up to 4 weeks.	Length of stay is the duration of a hospital stay in hours

Trial Locations

Locations (5)

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

Stollery Children's Hospital; 🇨🇦 Edmonton, Ontario, Canada

McMaster Children's Hospital; 🇨🇦 Hamilton, Ontario, Canada

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

CHU-Sainte Justine Hospital; 🇨🇦 Montreal, Quebec, Canada