Magnesium Trial in Acute Asthma in Emergency Department

NCT06785272 | Recruiting Phase 3 DMC

• 1 other identifier: 5274
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 6

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.

Conditions

Asthma

Keywords

asthma, magnesium sulfate; pediatric, acute asthma

Outcome Measures

Primary Outcomes (1)

• Pediatric Respiratory Assessment Measure (PRAM) score: This score ranges from 0-12. A score from 0-3 is mild, 4-7 moderate and 8-12 severe. A low score is a better outcome and a high score is a worse outcome.

  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. A PRAM score from 0-3 is mild, 4-7 moderate and 8-12 severe.

  The primary outcome measure will be the PRAM score at 120 minutes post start of experimental therapy.

Secondary Outcomes (9)

• Changes in PRAM score

  Changes in PRAM score from baseline (pre intervention) to 30, 60, 120, 180 minutes after start of experimental therapy

• Hospitalization for asthma at the index ED visit

  Up to 24 hours after starting experimental therapy

• Changes in respiratory rate

  From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention (respiratory rate )

• Changes in oxygen saturation

  From baseline (pre-intervention) to 30,60,120 and 180 minutes post intervention ( oxygen saturation)

• Changes in blood pressure

  From baseline (pre-intervention) to 10,20,30,60,120, and 180 minutes post intervention (blood pressure).

Study Arms (2)

Experimental Group

EXPERIMENTAL

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.

Drug: magnesium sulfate

Placebo Group

PLACEBO COMPARATOR

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.

Drug: Normal Saline

Interventions

magnesium sulfate 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) \[experimental group\]

Experimental Group

Normal Saline 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 \[control group\].

Placebo Group

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Receipt of IVMg within 24 hours prior to ED arrival.
• Known renal, chronic pulmonary, neurologic, cardiac or systemic disease: these may influence outcomes after Mg.
• Known hypersensitivity to Mg sulfate.
• Previous enrollment.
• Poor mastery of English and/or French language precluding informed consent understanding.
• No phone/email; unavailable for follow-up

Sponsors & Collaborators

• Suzanne Schuh: lead
• Alberta Children's Hospital: collaborator
• McMaster Children's Hospital: collaborator
• Stollery Children's Hospital: collaborator
• Children's Hospital of Eastern Ontario: collaborator
• St. Justine's Hospital: collaborator
• The Hospital for Sick Children: collaborator

Study Sites (6)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

NOT YET RECRUITING

Stollery Children's Hospital

Edmonton, Ontario, T6G 2B7, Canada

NOT YET RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, L8S 4L8, Canada

NOT YET RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

NOT YET RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

CHU-Sainte Justine Hospital

Montreal, Quebec, H3T 1C5, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Asthma

Interventions

Magnesium Sulfate; Saline Solution

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Suzanne Schuh, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sunita O'Shea

CONTACT

416-813-7654; sunita.oshea@sickkids.ca

Yaron Finkelstein, MD

CONTACT

416-813-7654; yaron.finkelstein@sickkids.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 21, 2025
• Study Start: October 8, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)