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

NCT ID: NCT07173855

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

3253 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-25

Study Completion Date

2027-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Critical Illness

Keywords

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Critical illness Magnesium Atrial fibrillation Protocols

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Pragmatic comparative effectiveness trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lower target (>0.7mmol)

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.

Group Type OTHER

Magnesium sulfate administration

Intervention Type DRUG

Magnesium sulfate is used in both arms for magnesium replacement.

Higher target (>0.95mmol/L)

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.

Group Type OTHER

Magnesium sulfate administration

Intervention Type DRUG

Magnesium sulfate is used in both arms for magnesium replacement.

Magnesium oxide

Intervention Type DRUG

In the higher-target arm, magnesium oxide 420mg po q12h x 2 is one of the options available for magnesium replacement when magnesium levels lie between 0.75 and 0.95mmol/L.

Magnesium glucoheptonate

Intervention Type DRUG

Magnesium glucoheptonate 30mL po q12h x 2 is an oral option for magnesium replacement in the higher-target arm.

Interventions

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Magnesium sulfate administration

Magnesium sulfate is used in both arms for magnesium replacement.

Intervention Type DRUG

Magnesium oxide

In the higher-target arm, magnesium oxide 420mg po q12h x 2 is one of the options available for magnesium replacement when magnesium levels lie between 0.75 and 0.95mmol/L.

Intervention Type DRUG

Magnesium glucoheptonate

Magnesium glucoheptonate 30mL po q12h x 2 is an oral option for magnesium replacement in the higher-target arm.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Scarborough Health Network

UNKNOWN

Sponsor Role collaborator

Lakeridge Health Corporation

OTHER

Sponsor Role collaborator

Scarborough General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Christopher Yarnell

Intensivist and Researcher

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Lakeridge Health Ajax-Pickering

Ajax, Ontario, Canada

Site Status NOT_YET_RECRUITING

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Site Status NOT_YET_RECRUITING

Scarborough Centenary Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Scarborough General Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Scarborough Birchmount Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Joshua Craig

Role: CONTACT

Phone: 4164382911

Email: [email protected]

Facility Contacts

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Joshua Craig

Role: primary

Joshua Craig

Role: primary

Joshua Craig

Role: primary

Other Identifiers

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ICU-25-018

Identifier Type: -

Identifier Source: org_study_id