Magnesium for Asthma

(MAGICIAN Trial)

Recruiting at 4 trial locations

Overseen By Yaron Finkelstein, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: The Hospital for Sick Children

Disqualifiers: Renal, Pulmonary, Neurologic, Cardiac, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 3 hours

192 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received intravenous magnesium within 24 hours before arriving at the emergency department.

What data supports the effectiveness of the drug Magnesium Sulfate for treating asthma?

Research shows that magnesium sulfate can help children and adults with severe asthma who don't respond well to initial treatments. It can improve breathing and reduce the need for hospital admission in these cases. ^{1 2 3 4 5}

Is magnesium sulfate safe for treating asthma?

Magnesium sulfate is generally considered safe and well-tolerated for treating severe asthma, with studies showing it is used effectively in both children and adults. It is often used as an additional treatment when standard therapies are not enough, and it is known to be inexpensive and effective. ^{2 3 6 7 8}

How is the drug magnesium sulfate different from other asthma treatments?

Magnesium sulfate is unique because it is used in emergency settings for acute severe asthma when other treatments like beta-agonists and corticosteroids are not effective. It works by relaxing the muscles around the airways, which can help improve breathing during severe asthma attacks. ^{3 4 9 10 11}

Research Team

Suzanne Schuh, MD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

This trial is for children with severe acute asthma who still have moderate to severe respiratory distress after one hour of initial emergency department therapy. It's not clear if they should be given magnesium sulfate (IVMg) or a placebo, as past studies are inconclusive about its benefits.

Inclusion Criteria

I am between 2 and 17 years old.

I have asthma diagnosed by a doctor and have responded to asthma treatments before.

My asthma is severe despite using salbutamol and ipratropium.

Exclusion Criteria

Need for airway support on arrival

I received IV magnesium within 24 hours before coming to the emergency department.

Known hypersensitivity to Mg sulfate

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Initial Emergency Department Therapy

Participants receive initial therapy with systemic corticosteroids and inhaled salbutamol and ipratropium

1 hour

1 visit (in-person)

Treatment

Participants receive a 30-minute IV infusion of magnesium sulfate or placebo, followed by monitoring for 3 hours

3 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including unscheduled asthma-related visits

72 hours

Treatment Details

Interventions

• Magnesium Sulfate

Trial Overview The study tests whether early IVMg treatment improves breathing difficulties in these children compared to a placebo. The main measure is the change in their Pediatric Respiratory Assessment Measure (PRAM) score at three hours after starting treatment.

Participant Groups

Group I: Experimental Group Experimental Treatment 1 Intervention

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 II: Placebo Group Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

McMaster Children's Hospital

Collaborator

Trials

43

Recruited

19,900+

St. Justine's Hospital

Collaborator

Trials

205

Recruited

87,300+

Children's Hospital of Eastern Ontario

Collaborator

Trials

134

Recruited

61,000+

Alberta Children's Hospital

Collaborator

Trials

58

Recruited

44,700+

Stollery Children's Hospital

Collaborator

Trials

25

Recruited

25,900+

Findings from Research

In a study of 54 children with moderate to severe asthma exacerbations, the administration of high-dose magnesium sulfate did not significantly improve asthma symptoms compared to a placebo, as measured by Pulmonary Index scores.

There was no notable difference in hospitalization rates or time to meet discharge criteria between the magnesium and placebo groups, indicating that magnesium sulfate may not be an effective routine treatment for acute asthma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of magnesium in the emergency department treatment of children with asthma. Scarfone, RJ., Loiselle, JM., Joffe, MD., et al.[2006]

A review of 8 studies involving 447 children found that prolonged magnesium sulfate infusions (over 1 hour) are used for treating refractory asthma, but most studies did not assess clinical outcomes like lung function or hospital admissions.

While magnesium sulfate infusions were generally safe, with only 1.1% of patients experiencing high magnesium levels, adverse events such as hypotension and nausea were more common in those receiving infusions lasting over 24 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Magnesium Sulfate Infusions for Status Asthmaticus in Children: A Systematic Review. Johnson, PN., Drury, AS., Gupta, N.[2022]

A review of 16 studies indicates that intravenous bolus magnesium sulphate is safe for treating children with acute severe asthma in non-critical care settings.

Safety measures, such as line of sight nursing and cardiorespiratory monitoring, are essential when administering magnesium sulphate to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is intravenous magnesium sulphate safe to be administered outside the critical care setting? de Havilland, A., Hariharan, G., Puvvadi, R.[2022]

Magnesium sulfate can be beneficial for asthmatic patients who do not respond well to initial treatments like beta-agonists and corticosteroids, potentially acting as a calcium antagonist and aiding in ion flux across cell membranes.

While routine use of magnesium sulfate in emergency departments for acute asthma is not recommended, it may provide some benefits as an adjunct therapy for severely ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of the intravenous and nebulized magnesium sulfate for the treatment of the acute asthma in the emergence]. Barbosa, FT., Barbosa, LT., Cunha, RM., et al.[2014]

References

1. India pubmed.ncbi.nlm.nih.gov

Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy. [2004]

2. Australia pubmed.ncbi.nlm.nih.gov

Intravenous magnesium sulfate in acute severe asthma. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

IV magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

A randomized trial of magnesium in the emergency department treatment of children with asthma. [2006]

5. United States pubmed.ncbi.nlm.nih.gov

High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Continuous Magnesium Sulfate Infusions for Status Asthmaticus in Children: A Systematic Review. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Survey of physicians' attitudes toward the use of magnesium sulfate for acute asthma exacerbations in Turkey. [2017]

8. Australia pubmed.ncbi.nlm.nih.gov

Is intravenous magnesium sulphate safe to be administered outside the critical care setting? [2022]

9. Brazil pubmed.ncbi.nlm.nih.gov

[Use of the intravenous and nebulized magnesium sulfate for the treatment of the acute asthma in the emergence]. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Effect of MgSO₄ on FEV₁ in stable severe asthma patients with chronic airflow limitation. [2016]

11. United States pubmed.ncbi.nlm.nih.gov

Lack of effectiveness of magnesium in chronic stable asthma. A prospective, randomized, double-blind, placebo-controlled, crossover trial in normal subjects and in patients with chronic stable asthma. [2019]