Clinical trial NCT05166811: Timely Intravenous Magnesium for Asthma in Children
Official title: Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: asthma
IV Magnesium
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
name: Nationwide Children's Hospital
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-12-22
Enrollment: 52
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Enrollment
timeFrame: 7 months of enrollment.
Secondary outcomes:
measure: Hospitalization
timeFrame: Actual disposition from chart review 1 week after enrollment.
measure: Hospitalization Anticipated by Treating Physician 2 Hours After Start of Study Infusion
timeFrame: Physician-anticipated hospitalization 2 hours after the start of study drug infusion
measure: Adverse Events and Safety Profiles - Hypotension and Perfusion
timeFrame: 2 hours after study drug infusion.
measure: Rescue Therapies Used During ED Care - SQ or IM Epinephrine
timeFrame: One week after enrollment
measure: Return ED Visit
timeFrame: Within 10 days after ED discharge
measure: Baseline Serum Magnesium
timeFrame: At IV placement before infusion of study drug
measure: Baseline Ionized Magnesium
timeFrame: At IV placement before infusion of study drug
measure: Post-infusion Serum Magnesium 1
timeFrame: 20-40 minutes after the start of study drug infusion
measure: Post-infusion Ionized Magnesium 1
timeFrame: 20-40 minutes after the start of study drug infusion
measure: Post-infusion Serum Magnesium 2
timeFrame: 90-150 minutes after the start of study drug infusion
measure: Post-infusion Ionized Magnesium 2
timeFrame: 90-150 minutes after the start of study drug infusion
measure: Rescue Therapies Used During ED Care - IV Epinephrine
timeFrame: One week after enrollment
measure: Rescue Therapies Used During ED Care - IV Terbutaline
timeFrame: One week after enrollment
measure: Rescue Therapies Used During ED Care - IV Magnesium
timeFrame: One week after enrollment
measure: Adverse Events and Safety Profiles - Supraventricular Tachycardia
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Abdominal Discomfort
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Vomiting
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Fatigue
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Hypokalemia
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Delirium
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Hypoxia
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Respiratory Distress
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Metabolic Acidosis
timeFrame: 1 week
measure: Adverse Events and Safety Profiles - Duodenal Ulcer Perforation
timeFrame: 1 week
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
Study officials:
References: