Magnesium Trial in Acute Asthma in Emergency Department

NCT ID: NCT06785272

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-08
• Study Completion Date: 2027-10-31

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 2 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: IV Mg 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 (ipratropium use as per local practice), 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.

Conditions

Asthma

Keywords

asthma, magnesium sulfate; pediatric, acute asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental Group

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.

Group Type: EXPERIMENTAL

magnesium sulfate

Intervention Type: DRUG

After initial therapy with the systemic 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) \[experimental group\]

Placebo Group

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.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

After initial therapy with the systemic 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 0.9% saline \[control group\].

Interventions

magnesium sulfate

After initial therapy with the systemic 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) \[experimental group\]

Intervention Type: DRUG

Normal Saline

After initial therapy with the systemic 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 0.9% saline \[control group\].

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 2.00-17.99 years (prior to 18th birthday),

2. Diagnosis of asthma, defined as an asthma or probable asthma diagnosis/asthma-like phenotype made by a physician (this includes ED physician) in a patient who in the opinion of the treating ED physician requires therapy for acute asthma in the ED (GINA asthma guidelines, 2024).

3. Moderate-severe asthma after initial therapy with 3 treatments of inhaled salbutamol and ipratropium, defined as an eligibility PRAM ≥5, indicating a strong association with hospitalization.

Exclusion Criteria

1. Receipt of IVMg within 24 hours prior to ED arrival.

3. Known renal, chronic pulmonary, neurologic, cardiac or systemic disease: these may influence outcomes after Mg.

4. Known hypersensitivity to Mg sulfate.

5. Previous enrollment.

6. Poor mastery of English and/or French language precluding informed consent understanding.

7. No phone/email; unavailable for follow-up

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alberta Children's Hospital

OTHER

Sponsor Role: collaborator

McMaster Children's Hospital

OTHER

Sponsor Role: collaborator

Stollery Children's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Eastern Ontario

OTHER

Sponsor Role: collaborator

St. Justine's Hospital

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: collaborator

Suzanne Schuh

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Schuh

Staff Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Suzanne Schuh, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status: NOT_YET_RECRUITING

Stollery Children's Hospital

Edmonton, Ontario, Canada

Site Status: NOT_YET_RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, Canada

Site Status: NOT_YET_RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status: NOT_YET_RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status: RECRUITING

CHU-Sainte Justine Hospital

Montreal, Quebec, Canada

Site Status: NOT_YET_RECRUITING

Countries

Canada

Central Contacts

Sunita O'Shea

Role: CONTACT

Phone: 416-813-7654

Email: sunita.oshea@sickkids.ca

Yaron Finkelstein, MD

Role: CONTACT

Phone: 416-813-7654

Email: yaron.finkelstein@sickkids.ca

Facility Contacts

Mohamed Eltorki, MD

Role: primary

Stephen Freedman, MD

Role: backup

Sarah Curtis, MD

Role: primary

Andrew Dixon, MD

Role: backup

April Kam, MD

Role: primary

Redjana Carciumaru

Role: backup

Waleed Alqurashi, MD

Role: primary

Candice McGahern

Role: backup

Sunita O'Shea Project Manager

Role: primary

Jocelyn Gravel, MD

Role: primary

Ramona Cook, BScN

Role: backup

Other Identifiers

5274

Identifier Type: -

Identifier Source: org_study_id