JMIR Publications

ABSTRACT

Background:

Children managed for asthma in an emergency department (ED) may be less likely to be hospitalized if they receive intravenous magnesium sulfate (IVMg). Asthma guidelines recommend IVMg for severely sick children but note a lack of evidence to support this recommendation. All prior trials of IVMg in children with asthma have been too small to answer whether IVMg is effective and safe. A few major questions remain about IVMg. First, it has not been tested early in the course of ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a known adverse effect of IVMg, is not well characterized in prior research. Third, no trials have compared different IVMg doses or serial serum magnesium concentrations to optimize dosing, so the most effective dose is unknown. A conclusive large randomized, placebo-controlled clinical trial of IVMg might be challenging due to the need to enroll and complete study procedures quickly, a lack of understanding of blood pressure changes after IVMg, and lack of pharmacologic information to guide the optimal doses of IVMg to be tested. Therefore, a pilot study to inform the above gaps is warranted prior to conducting a definitive trial.

Objective:

The objectives of this study are to: 1. Demonstrate the feasibility of enrolling children with severe acute asthma in the ED in a multicenter, randomized, controlled trial of placebo, low-dose IVMg, or high-dose IVMg. 2. Demonstrate the feasibility of timely delivery of study medication, assessment of blood pressure, and evaluation of adverse events in a standardized protocol. 3. Externally validate a previously constructed pharmacokinetic (PK) model and develop a combined pharmacokinetic/pharmacodynamic (PK/PD) model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of efficacy and safety.

Methods:

This pilot trial tests procedures and gathers information to plan a definitive trial. The pilot trial has enrolled 43 children and will enroll as many as 90 children across three sites and randomize each child to one of three study arms, measure blood pressure frequently, and collect three blood samples from each participant with corresponding clinical asthma scores.

Results:

The project was funded by the National Heart, Lung, and Blood Institute (1 R34HL152047-2) in March 2022, began enrollment in September 2022, and we will submit results for publication in late 2023.

Conclusions:

The results of this study will guide the planning of a large definitive multi-center trial powered to evaluate if IVMg reduces hospitalization. Blood pressure measurements will inform a monitoring plan for the larger trial, and blood samples and asthma scores will be used to validate pharmacologic models to select the optimal dose of IVMg to be evaluated in the definitive trial. Clinical Trial: ClinicalTrials.gov Identifier: NCT05166811