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): 140
• 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
    • 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

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 a critical care unit with EITHER:

   1. Non-invasive ventilation (including high flow nasal canula) or invasive mechanical ventilation with an expected duration >24 hours AND/OR
   2. Vasopressor or ionotropic support for shock of any etiology. Shock is defined by the need for one of the following vasopressors/inotropes:

   Dopamine Dobutamine Norepinephrine Epinephrine Ephedirine Milrinone at any dose (if used in conjunction with another agent) Vasopressin (if used in conjunction with another agent)

3. Receiving continuous cardiac monitoring.

Exclusion Criteria:

1. >12 hours from ICU admission
2. Active atrial fibrillation prior to randomization or pre-existing (permanent or paroxysmal) atrial fibrillation
3. Unlikely to survive >24 hours or palliative patients
4. Cardiac surgery patients
5. Patients requiring parenteral magnesium therapy (e.g. pre-eclampsia, asthma)
6. Transfer from another ICU
7. Patients receiving dialysis
8. Positive pregnancy test
9. Previously enrolled in this trial
10. 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	1) Protocol adherence ≥ 90% (We define protocol adherence as administration of first dose of study drug within 12 hours starting supported ventilation or vasoactive medications, delivery of all additional doses of study drugs for the following 4 days in patients who do not meet any stopping criteria, including patients transferred to the ward)	90 days
RCT Feasibility	2) Recruitment rate of ≥ 6 patients/month (2 patient/month/ICU)	90 days
RCT Feasibility	3) CardioSTAT tolerance and use ≥ 90% (defined appropriate placement, uninterrupted wear, and returned monitors)	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Care Outcomes	Total number of patients developing NOAF within 14 days of enrolment	28 days
Acute Care Outcomes	Use of rate and rhythm controlling agents, vasoactive agents, diuretics, steroids, anticoagulants	28 days
Acute Care Outcomes	bleeding events	28 days
Acute Care Outcomes	thromboembolic events	28 days
Acute Care Outcomes	persistent organ disfunction	28 days
Acute Care Outcomes	mortality	28 days
Hospital Outcomes	Development of renal failure requiring dialysis	28 days
Hospital Outcomes	ICU length of stay	28 days
Hospital Outcomes	hospital length of stay	28 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: Queen's University
• Collaborators: 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, 2025
• Study Completion (Estimated): July 1, 2025

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 (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Prevention; Prophylaxis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Critical Illness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: ATOMIC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No