Timely Intravenous Magnesium for Asthma in Children

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05166811

Acronym

IMPACT-ED

Enrollment

Registered

2021-12-22

Start date

2022-09-12

Completion date

2023-07-31

Last updated

2024-12-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

asthma, IV Magnesium

Brief summary

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.

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.

Interventions

DRUGMagnesium 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.

DRUG0.9% 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Doses will be prepared ahead of time by an investigational pharmacist, arms will be identical in appearance, and clinicians administering the study drug will be blinded to the study arm the patient receives.

Intervention model description

Randomized, double-blind, placebo-controlled trial

Eligibility

Sex/Gender

ALL

Age

2 Years to 17 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Enrollment	7 months of 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.

Secondary

Measure	Time frame	Description
Hospitalization Anticipated by Treating Physician 2 Hours After Start of Study Infusion	Physician-anticipated hospitalization 2 hours after the start of study drug infusion	The treating clinician's stated disposition two hours after the start of study infusion.
Adverse Events and Safety Profiles - Hypotension and Perfusion	2 hours after study drug infusion.	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.
Rescue Therapies Used During ED Care - SQ or IM Epinephrine	One week after enrollment	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.
Return ED Visit	Within 10 days after ED discharge	In patients discharged from the ED, any ED visit and/or hospitalization following 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	One week after enrollment	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.
Hospitalization	Actual disposition from chart review 1 week after enrollment.	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.
Rescue Therapies Used During ED Care - IV Magnesium	One week after enrollment	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.
Adverse Events and Safety Profiles - Supraventricular Tachycardia	1 week	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.
Adverse Events and Safety Profiles - Abdominal Discomfort	1 week	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.
Adverse Events and Safety Profiles - Vomiting	1 week	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.
Adverse Events and Safety Profiles - Fatigue	1 week	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.
Adverse Events and Safety Profiles - Hypokalemia	1 week	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.
Adverse Events and Safety Profiles - Delirium	1 week	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.
Adverse Events and Safety Profiles - Hypoxia	1 week	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.
Adverse Events and Safety Profiles - Respiratory Distress	1 week	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.
Adverse Events and Safety Profiles - Metabolic Acidosis	1 week	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.
Adverse Events and Safety Profiles - Duodenal Ulcer Perforation	1 week	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.
Rescue Therapies Used During ED Care - IV Terbutaline	One week after enrollment	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.

Countries

United States

Participant flow

Recruitment details

The study was conducted at three sites within the Pediatric Emergency Care Applied Research Network (PECARN). The three enrolling sites are EDs at tertiary pediatric hospitals and are geographically and demographically diverse. Eligible participants were identified from children presenting to the ED for treatment of acute asthma. Screening occurred at sites from September 2022 through May 2023.

Participants by arm

Arm	Count
Placebo For the placebo arm, 40 mL of 0.9% sodium chloride solution was drawn into a polyvinylchloride container identical in appearance to the containers used for the IVMg arms. After randomization the institutional pharmacist prepared the dosage (1 mL/kg, with max of 40 mL) from previously prepared container. The dose was delivered by the clinical nurse over 20 minutes through a peripheral IV. 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.	18
50 mg/kg Doses for each IVMg arm were 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 was 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 prepared the dosage (1 mL/kg, with max of 40 mL) from previously prepared container. The dose was delivered by the clinical nurse over 20 minutes through a peripheral IV. Magnesium Sulfate, Heptahydrate: A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line.	17
75 mg/kg Doses for each IVMg arm were 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 was 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 prepared the dosage (1 mL/kg, with max of 40 mL) from previously prepared container. The dose was by the clinical nurse over 20 minutes through a peripheral IV. Magnesium Sulfate, Heptahydrate: A single dose of intravenous magnesium sulfate given over 20 minutes through a peripheral intravenous line.	17
Total	52

Baseline characteristics

Characteristic	75 mg/kg	Total	Placebo	50 mg/kg
Age, Continuous	7.3 years STANDARD_DEVIATION 4.3	7.3 years STANDARD_DEVIATION 6.4	7.0 years STANDARD_DEVIATION 5.9	7.4 years STANDARD_DEVIATION 7.4
Age, Customized Age	5.8 years	6.4 years	5.9 years	7.4 years
Age, Customized Age Group 2-4 years	6 Participants	17 Participants	7 Participants	4 Participants
Age, Customized Age Group 5-17 years	11 Participants	33 Participants	10 Participants	12 Participants
Age, Customized Age Group Unknown	0 Participants	2 Participants	1 Participants	1 Participants
Arrival pulse oximeter reading 91% or lower	7 Participants	23 Participants	9 Participants	7 Participants
Arrival pulse oximeter reading 92-94%	6 Participants	16 Participants	5 Participants	5 Participants
Arrival pulse oximeter reading 95% or higher	4 Participants	13 Participants	4 Participants	5 Participants
ED visit for asthma in the last 12 months	14 Participants	35 Participants	9 Participants	12 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	8 Participants	3 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants	40 Participants	13 Participants	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	4 Participants	2 Participants	1 Participants
Parent with asthma	12 Participants	34 Participants	12 Participants	10 Participants
Parent with eczema	8 Participants	22 Participants	6 Participants	8 Participants
Parent with seasonal allergies	12 Participants	33 Participants	10 Participants	11 Participants
Personal history of anaphylaxis	1 Participants	5 Participants	2 Participants	2 Participants
Personal history of eczema	6 Participants	23 Participants	8 Participants	9 Participants
Personal history of prematurity	5 Participants	12 Participants	5 Participants	2 Participants
Prescribed a daily controller medication	17 Participants	52 Participants	18 Participants	17 Participants
Prior hospitalizations for asthma	14 Participants	35 Participants	9 Participants	12 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	3 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	6 Participants	19 Participants	5 Participants	8 Participants
Race (NIH/OMB) More than one race	1 Participants	2 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	5 Participants	1 Participants	2 Participants
Race (NIH/OMB) White	4 Participants	20 Participants	10 Participants	6 Participants
Sex/Gender, Customized Sex Female	5 Participants	15 Participants	5 Participants	5 Participants
Sex/Gender, Customized Sex Male	12 Participants	35 Participants	12 Participants	11 Participants
Sex/Gender, Customized Sex Unknown	0 Participants	2 Participants	1 Participants	1 Participants
Taking controller medication 4+ days a week	7 Participants	25 Participants	8 Participants	10 Participants
Weight	18.1 kilograms	21.1 kilograms	20.8 kilograms	28.4 kilograms

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 18	0 / 16	0 / 15
other Total, other adverse events	4 / 18	5 / 16	6 / 15
serious Total, serious adverse events	2 / 18	0 / 16	0 / 15

Outcome results

Primary

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.

Time frame: 7 months of enrollment.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo	Enrollment	18 Participants
50 mg/kg	Enrollment	17 Participants
75 mg/kg	Enrollment	17 Participants

Secondary

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.

Time frame: 1 week