Timely Intravenous Magnesium for Asthma in Children

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: Magnesium Sulfate, Heptahydrate
Drug: 0.9% saline

Registration Number: NCT05166811

Lead Sponsor: University of Utah

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 52

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
50 mg/kg	Magnesium Sulfate, Heptahydrate	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.
75 mg/kg	Magnesium Sulfate, Heptahydrate	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.
Placebo	0.9% saline	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
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
Baseline Ionized Magnesium	At IV placement before infusion of study drug
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.
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.
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.

Trial Locations

Locations (3): Nationwide Children's Hospital
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Columbus, Ohio, United States
Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States
Primary Children's Hospital
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Salt Lake City, Utah, United States