Magnesium Prophylaxis for the Prevention of New-Onset Atrial Fibrillation in Critically Ill Patients (ATOMIC)

Parenteral Magnesium Prophylaxis for the Prevention of New-Onset Atrial Fibrillation in Critically Ill Patients - a Pilot Feasibility Study

A double-blind, multi-centre, randomized, placebo-controlled, feasibility pilot trial in the prevention of new onset atrial fibrillation of critically ill patients admitted to an ICU.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; New Onset Atrial Fibrillation
• Intervention / Treatment: Drug: Placebo; Drug: Magnesium sulfate

Detailed Description

Most studies of new onset atrial fibrillation (NOAF) in critical illness focus on treatment of this arrhythmia but this innovative study will focus on prevention. Parenteral Mg is a low cost and readily available treatment that may be beneficial for reducing the incidence of NOAF in critically ill patients, with the potential to improve patient centred outcomes and provide a cost effective prophylaxis. The main outcome of this study is to determine if it is feasible to conduct a randomized controlled trial comparing parenteral magnesium sulfate with placebo for the prophylaxis of new onset atrial fibrillation in critically ill patients.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Miranda Hunt; Phone Number: 3190 613 549 6666; Email: miranda.hunt@kingstonhsc.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y3
      • Not yet recruiting
      • St Joseph's Healthcare Hamilton
      • Contact: Dr. Deborah Cook, MD
    • Kingston, Ontario, Canada, K7L2V7
      • Recruiting
      • Kingston Health Sciences Centre
      • Principal Investigator: Stephanie Sibley, MD
      • Contact: Miranda Hunt; Phone Number: 3190 613 549 9999; Email: miranda.hunt@kingstonhsc.ca
    • Ottawa, Ontario, Canada, K1H 8L6
      • Not yet recruiting
      • The Ottawa Hospital - General Campus
      • Contact: Dr. Andrew Seely, MD
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Not yet recruiting
      • The Ottawa Hospital - Civic Campus
      • Contact: Andrew Seely, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥18 years;

2. Admitted to an ICU with one or more of the following:

   1. Non-invasive ventilation (including CPAP, Bipap and high flow oxygen (>10L/min) or invasive mechanical ventilation with an expected duration >24 hours for respiratory failure (hypercarbic or hypoxic)
   2. Vasopressor or inotropic support with an expected duration of >24 hours
   3. Cardiac arrest
3. Continuous cardiac monitoring.

Exclusion Criteria

1. Receiving ICU intervention (Non-invasive ventilation (including high flow nasal canula), invasive mechanical ventilation or inotropic support) for >18 hours
2. Receiving IMV for airway protection only (for example, isolated head trauma)
3. Active atrial fibrillation at the time of enrolment
4. On oral or continuous infusion of Amiodarone
5. Unlikely to survive >24 hours or palliative patients
6. Cardiac surgery patients
7. Patients requiring parenteral magnesium therapy (e.g. pre-eclampsia, asthma)
8. Patients receiving dialysis
9. Positive pregnancy test (females <50 years old)
10. Previously enrolled in this trial
11. Treating physician refuses enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnesium Sulfate; 4g Magnesium sulfate (100mL) BID, given intravenously over 2 hours, for a total of 10 doses	Drug: Magnesium sulfate; Intravenous Magnesium sulfate
Placebo Comparator: 0.9% NaCl; 100mL 0.9% NaCl BID, given intravenously over 2 hours, for a total of 10 doses	Drug: Placebo; 0.9% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RCT Feasibility	To assess feasibility of patient recruitment, randomization procedures, intervention and data collection and measure protocol adherence. Protocol adherence ≥ 90% (We define protocol adherence as administration of first dose of study drug within 18 hours (+1hr window) of 1st ICU intervention (life sustaining therapy) delivery of all additional	90 days
RCT Feasibility	Recruitment rate of ≥ 2 patients/month/ICU	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Equipoise and Feasibility	Physician willingness to recruit patients in the setting of existing electrolyte replacement protocols; effectiveness of blinding; proportion of patients who meet eligibility criteria of those admitted to ICU; proportion of eligible patients for whom consent is obtained; proportion of patients who re-consent when they regain capacity for those randomized under the deferred consent model; proportion of patients lost to follow-up; time for research personnel to complete study related tasks.	365 days
Acute Care Outcomes	Total number of patients developing AF within 28 days of enrolment (AF will be defined as at least 30 seconds of NOAF detected by cardiac monitoring or ECG); Use of rate and rhythm controlling agents, vasoactive agents, diuretics, steroids, anticoagulants, bleeding events, thromboembolic events (as defined in the 2018 Canadian Stroke Best Practices Guideline1; these will be adjudicated by a neurologist blinded to study groups), persistent organ dysfunction, mortality	28 days
Hospital Outcomes	Days alive and ventilator free, ICU length of stay, and hospital length of stay.	28 days
Adverse Events	Adverse drug reactions including bradycardia (HR <60 bpm); severe bradycardia (HR <50 bpm); clinically significant bradycardia (bradycardia requiring inotropes, vasopressors, external pacing, temporary pacemaker, or discontinuation of the trial medication); hypotension (MAP< 65mmHg, or systolic blood pressure [SBP]>20mmHg below admission baseline); clinically significant hypotension (hypotension requiring vasopressors, fluid administration, or discontinuation of the trial medication) while the study drug is being infused.	28 days
Functional Outcomes	EQ-5D score, death after discharge.	365 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse patch reactions (skin irritation)	90 days
Adverse Events	bradycardia (HR <60 bpm); severe bradycardia (HR <50 bpm); clinically significant bradycardia (bradycardia requiring inotropes, vasopressors, external pacing, temporary pacemaker, or discontinuation of the trial medication)	90 days
Adverse Events	hypotension (MAP< 65mmHg, or systolic blood pressure [SBP]>20mmHg below admission baseline); clinically significant hypotension (hypotension requiring vasopressors, fluid administration, or discontinuation of the trial medication)	90 days
Functional Outcomes	Clinical Frailty Score	365 days
Functional Outcomes	EuroQoL EQ-5D	365 days
Functional Outcomes	death after discharge	365 days

Collaborators and Investigators

• Sponsor: Dr. Stephanie Sibley
• Collaborators: Canadian Institutes of Health Research (CIHR); Southeastern Ontario Academic Medical Organization (SEAMO)
• Investigators: Principal Investigator: Stephanie Sibley, MD, Queen's University

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Prevention; Prophylaxis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Critical Illness; Sulfur Compounds; Inorganic Chemicals; Sulfur Acids; Sulfates; Sulfuric Acids; Magnesium Compounds; Magnesium Sulfate
• Other Study ID Numbers: ATOMIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No