Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED): Protocol for a Multicenter Pilot Randomized Controlled Trial

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 previous 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, has not been well characterized in previous research. Third, no trials have compared different IVMg doses or serial serum magnesium (total and ionized) concentrations to optimize dosing, so the most effective dose is unknown. A large, conclusive, 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 a 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 before 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 a 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; and (3) externally validate a previously constructed pharmacokinetic model and develop a combined pharmacokinetic/pharmacodynamic 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 will enroll as many as 90 children across 3 sites, randomize each child to 1 of 3 study arms, measure blood pressure frequently, and collect 3 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. Enrollment began in September 2022, and 43 children have been enrolled as of April 2023. We will submit the results for publication in late 2023. CONCLUSIONS: The results of this study will guide the planning of a large, definitive, multicenter 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05166811; https://clinicaltrials.gov/ct2/show/NCT05166811 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48302