Effect of Protocolized Magnesium Replacement on Mortality and Atrial Fibrillation in Critically Ill Patients (MAGNOLIA)

Scarborough General Hospital

Status and phase: Enrolling; Phase 4

Conditions: Critical Illness

Treatments: Drug: Magnesium oxide; Drug: Magnesium glucoheptonate; Drug: Magnesium sulfate administration

Study type: Interventional

Funder types: Other

Identifiers

NCT07173855

ICU-25-018

Details and patient eligibility

About

In patients with critical illness, such as severe infections, heart attacks, or respiratory failure, most intensive care units (ICUs) measure magnesium levels and give supplemental doses of magnesium when levels are below certain targets. However, the best targets are unknown. The goal of this clinical trial is to study protocols for magnesium supplementation in people with critical illness, comparing a protocol with higher target level to a protocol with a lower target level.

The main question this study aims to answer is whether magnesium supplementation protocols targeting a higher or lower level lead to better 30-day survival and less atrial fibrillation.

Participants will not have to do any specific tasks, undergo any additional tests, or complete any surveys.

Full description

Background: Measurement of serum magnesium levels, and administration of supplemental magnesium when levels are below target, is a common element of routine care for critically ill patients. However, targets for replacement vary, and the targets that lead to the best outcomes are unknown.

Methods: Multi-center open-label parallel group randomized controlled superiority trial of adult critically ill patients receiving protocolized magnesium replacement, comparing a higher target (>0.95mmol/L) to a lower target (>0.7mmol/L). The trial will be embedded into the electronic medical record (EMR) at 5 hospitals across 2 health networks in Ontario, Canada, with a shared EMR. Patients aged 16 years or older who have ICU admission orders and an order for the magnesium replacement protocol will be included. Patients with pre-eclampsia, sustained ventricular tachycardia, or neuromuscular junction disease will be excluded. The primary outcome will be an ordinal composite, evaluated at 30 days, composed of death and the number of days free of atrial fibrillation or flutter in ICU. Secondary outcomes will include ventricular arrhythmia and antiarrhythmics administered; receipt of vasopressors, ventilation, and new renal replacement therapy in ICU; lengths of ICU and hospital stay; hospital mortality at 60 and 90 days, magnesium levels, and magnesium supplementation. Analyses will use Bayesian regression with weakly skeptical priors and an intention-to-treat approach. Because both targets lie within the standard of care, the trial will use opt-out consent. Screening will be integrated with the EMR, such that when a patient meets inclusion criteria, a pop-up will appear for the ordering clinician. After the clinician confirms eligibility, the patient will be randomized and assigned to their target. Outcome ascertainment will occur within the EMR.

Discussion: This randomized controlled trial addresses an important uncertainty regarding routine care in the ICU with an EMR-embedded design. The innovative EMR-embedded design facilitates the large sample sizes and comprehensive, equitable recruitment needed for a trial evaluating a routine care intervention, and will lead to seamless integration with routine care upon trial completion.

Enrollment: 3,253 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 16 years or older
• Admission orders written to a medical-surgical intensive care unit at a participating site
• Magnesium replacement protocol ordered

Exclusion criteria

• Prior enrollment in or withdrawal from MAGNOLIA trial
• Sustained ventricular tachycardia
• Pre-eclampsia
• Myasthenia gravis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,253 participants in 2 patient groups

Lower target (>0.7mmol)

Other group

Description:

Protocolized magnesium replacement according to magnesium level as follows: for 0.45 - 0.70mmol/L, magnesium sulfate 4g IV x 1 and repeat magnesium level the next day; for \< 0.45mmol/L, magnesium sulfate 6g IV x 1, alert most responsible physician, and repeat level in 4 hours.

Treatment:

Drug: Magnesium sulfate administration

Higher target (>0.95mmol/L)

Other group

Description:

Protocolized magnesium replacement according to magnesium level as follows: for 0.75-0.95mmol/L, magnesium sulfate 2g IV x 1, magnesium oxide 420 mg po q12h x 2, or magnesium glucoheptonate 30mL po q12h x 2; for 0.45 - 0.74mmol/L, magnesium sulfate 4g IV x 1 and repeat magnesium level the next day; for \< 0.45mmol/L, magnesium sulfate 6g IV x 1, alert most responsible physician, and repeat level in 4 hours.

Treatment:

Drug: Magnesium glucoheptonate

Drug: Magnesium sulfate administration

Drug: Magnesium oxide