Magnesium Trial in Acute Asthma in Emergency Department (MAGICIAN)

The Hospital for Sick Children

Status and phase: Not yet enrolling; Phase 3

Conditions: Asthma

Treatments: Drug: magnesium sulfate; Drug: Normal Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT06785272

5128

Details and patient eligibility

About

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.

Full 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.

Enrollment: 192 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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192 participants in 2 patient groups, including a placebo group

Experimental Group

Experimental group

Description:

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.

Treatment:

Drug: magnesium sulfate

Placebo Group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Normal Saline