Timely Intravenous Magnesium for Asthma in Children (IMPACT-ED)

Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department

Many children currently being hospitalized with severe asthma could potentially avoid hospitalization and be sent home if their treatment in the emergency department was more effective. The investigators will conduct a pilot trial that will lead to a larger study to conclusively answer whether a simple and inexpensive medicine, intravenous magnesium sulfate, can be used in the emergency department to prevent hospitalization for these children.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Magnesium Sulfate, Heptahydrate; Drug: 0.9% saline

Detailed Description

5.4.1 Acquisition The specific study agent to be used in this pilot trial is Magnesium Sulfate in Water for Injection, a sterile, nonpyrogenic solution of magnesium sulfate heptahydrate in water. Study agent will be acquired by each hospital's research pharmacy from Pfizer, Inc as a solution of magnesium sulfate in water at 80 mg/mL. Agent will be shipped directly from Pfizer to each study hospital pharmacy.

5.4.2 Preparation, Storage & Labeling Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of Intravenous Magnesium Sulfate (IVMg) from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 50 mg/kg arm, this will be accomplished by mixing 25 mL of IVMg (80 mg/mL) with 15 mL of sterile water for a final concentration of 50 mg/mL and volume of 40 mL. For the 75 mg/kg arm, this will be accomplished by mixing 37.5 mL of IVMg (80 mg/mL) with 2.5 mL of sterile water for a final concentration of 75 mg/mL and volume of 40 mL. For the placebo arm, 40 mL of 0.9% sodium chloride solution will be drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. Each prepared dose will be labeled according to the sequential randomization scheme and stored according to local pharmacy procedure. Unused doses prepared locally will be replaced after one week of storage.

5.4.3 Dosing Schedule

After randomization the institutional pharmacist will draw equivolumetric dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. Enrolled subjects will be randomized to one of three arms:

• IVMg 75 mg/kg arm: 75 mg/kg (max 3 gm) infused over 20 minutes through a peripheral IV catheter
• IVMg 50 mg/kg arm: 50 mg/kg (max 2 gm) infused over 20 minutes through a peripheral IV catheter
• Placebo arm: 1 mL/kg (max 40 ml) of normal saline over 20 minutes through a peripheral IV catheter 5.4.4 Dose Modification for Potential Toxicity Clinicians will not administer IVMg to enrolled subjects outside of the study protocol until study outcomes have been determined 2 hours after the start of the infusion. The half-life of IVMg is approximately 2 hours.49 Repeated-dose protocols in an ICU setting that gave as much as 125 mg/kg IVMg to children with asthma over two hours produced no hypotension or other serious adverse effects.47 Because of this margin of safety, open-label IVMg 50 mg/kg can be administered safely 2 hours after the study infusion under strict study monitoring protocols without need for unblinding.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Utah
    • Salt Lake City, Utah, United States, 84010
      • Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria are:

1. A prior physician diagnosis of asthma confirmed by a treating physician in the ED who has spoken with the patient and family and reviewed the medical record (ED attending or fellow physician)
2. Severe acute asthma, defined as a Pediatric Respiratory Assessment Measure (PRAM) score of 7 or greater as assessed by a treating physician at the time of screening using the study scoring instrument, which takes 60 seconds to complete
3. Children 2-17 years of age

Exclusion criteria are:

• Known pregnancy (by patient or parent report) or positive pregnancy test on females 12 years of age and older
• Age-adjusted hypotension at presentation using age-based Pediatric Advanced Life Support parameters (children >1 year to 10 years, systolic blood pressure (SBP)<(70 + 2 x age in years); >10 years, SBP < 90 mmHg)71
• Known severe renal impairment (by parent or patient report)
• Application of assisted ventilation before enrollment assessment (intubated, bi-level positive airway pressure, continuous positive airway pressure)
• Received IVMg within 24 hours prior to screening (by parent or patient report or medical record review)
• Enrollment assessment is 60 minutes after the start of ED treatment (start of first albuterol treatment)
• Previous enrollment in the same trial (by research coordinator review of trial records)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 75 mg/kg; Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of IVMg from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 75 mg/kg arm, this will be accomplished by mixing 37.5 mL of IVMg (80 mg/mL) with 2.5 mL of sterile water for a final concentration of 75 mg/mL and volume of 40 mL. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.	Drug: Magnesium Sulfate, Heptahydrate; A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line. Two arms of the study will deliver intravenous magnesium, one at a dose of 50 mg/kg, and the other at a dose of 75 mg/kg.; Other Names: Intravenous magnesium sulfate
Active Comparator: 50 mg/kg; Doses for each IVMg arm will be prepared in identical manner, by drawing a specified volume of IVMg from the commercial container using sterile technique and mixing in a polyvinylchloride container with a specified volume of sterile water. For the 50 mg/kg arm, this will be accomplished by mixing 25 mL of IVMg (80 mg/mL) with 15 mL of sterile water for a final concentration of 50 mg/mL and volume of 40 mL. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.	Drug: Magnesium Sulfate, Heptahydrate; A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line. Two arms of the study will deliver intravenous magnesium, one at a dose of 50 mg/kg, and the other at a dose of 75 mg/kg.; Other Names: Intravenous magnesium sulfate
Placebo Comparator: Placebo; For the placebo arm, 40 mL of 0.9% sodium chloride solution will be drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. After randomization the institutional pharmacist will draw dosages (1 mL/kg, with max of 40 mL) from previously prepared vials. The dose will be delivered by the clinical nurse over 20 minutes through a peripheral IV.	Drug: 0.9% saline; A single dose of intravenous 0.9% sodium chloride given over 20 minutes through a peripheral intravenous line as the placebo arm of the study.; Other Names: normal saline; 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrollment	The primary outcome in this pilot trial is demonstration of the ability to enroll severely ill children with asthma in a randomized trial requiring timely delivery of IVMg or placebo. The investigators anticipate that the primary outcome of the future large trial will be the proportion of children hospitalized at the index visit in each arm.	7 months of enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization	Actual patient disposition from medical record review after completion of ED treatment. Hospitalization will be defined as any outcome other than discharge from the ED, including hospitalization in an ICU, hospital unit, or observation area.	Actual disposition from chart review 1 week after enrollment.
Hospitalization Anticipated by Treating Physician 2 Hours After Start of Study Infusion	The treating clinician's stated disposition two hours after the start of study infusion.	Physician-anticipated hospitalization 2 hours after the start of study drug infusion
Adverse Events and Safety Profiles - Hypotension and Perfusion	Decrease in blood pressure was categorized based on degree of associated symptoms and defined as occurring less than 2 hours after the start of study drug infusion or 2 hours and later. Hypotension is defined by age-based Pediatric Advanced Life Support guidelines.	2 hours after study drug infusion.
Rescue Therapies Used During ED Care - SQ or IM Epinephrine	Count of the number of participants that were administered subcutaneous (SQ) or intramuscular (IM) epinephrine while in the ED during the index visit, recorded by chart review approximately one week after enrollment.	One week after enrollment
Return ED Visit	In patients discharged from the ED, any ED visit and/or hospitalization following discharge.	Within 10 days after ED discharge
Baseline Serum Magnesium		At IV placement before infusion of study drug
Baseline Ionized Magnesium		At IV placement before infusion of study drug
Post-infusion Serum Magnesium 1		20-40 minutes after the start of study drug infusion
Post-infusion Ionized Magnesium 1		20-40 minutes after the start of study drug infusion
Post-infusion Serum Magnesium 2		90-150 minutes after the start of study drug infusion
Post-infusion Ionized Magnesium 2		90-150 minutes after the start of study drug infusion
Rescue Therapies Used During ED Care - IV Epinephrine	Count of the number of participants that were administered intravenous (IV) epinephrine while in the ED during the index visit, recorded by chart review approximately one week after enrollment.	One week after enrollment
Rescue Therapies Used During ED Care - IV Terbutaline	Count of the number of participants that were administered intravenous (IV) terbutaline while in the ED during the index visit, recorded by chart review approximately one week after enrollment.	One week after enrollment
Rescue Therapies Used During ED Care - IV Magnesium	Count of the number of participants that were administered intravenous (IV) magnesium while in the ED during the index visit aside from any study infusion administered, recorded by chart review approximately one week after enrollment.	One week after enrollment
Adverse Events and Safety Profiles - Supraventricular Tachycardia	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Abdominal Discomfort	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Vomiting	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Fatigue	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Hypokalemia	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Delirium	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Hypoxia	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Respiratory Distress	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Metabolic Acidosis	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week
Adverse Events and Safety Profiles - Duodenal Ulcer Perforation	Adverse events were assessed through chart review and phone call with the parent of the participant one week after enrollment. Timing after start of study infusion was not recorded.	1 week

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Children's Hospital of Philadelphia; National Heart, Lung, and Blood Institute (NHLBI); Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: asthma; IV Magnesium
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Reproductive Control Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Anti-Arrhythmia Agents; Membrane Transport Modulators; Anticonvulsants; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: IRB 104082; 1R34HL152047-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No