Timely Intravenous Magnesium for Asthma in Children
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

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 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.
    

Intervention name(s): Magnesium Sulfate, Heptahydrate; 0.9% saline
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): Intravenous magnesium sulfate; normal saline; 0.9% sodium chloride
Intervention MeSH terms: Magnesium Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, placebo-controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: asthma; IV Magnesium