Peri-Operative Magnesium Infusion to Prevent Atrial Fibrillation Evaluated. (POMPAE)

Randomized Controlled Trial of Magnesium Sulfate Versus Placebo on the Prevention of Atrial Fibrillation Post Cardiac Surgery.

Post-operative atrial fibrillation (POAF) is commonly observed in patients post cardiac surgery without a previous history of atrial fibrillation (AF) or other arrythmias. It's associated with significant postoperative complications including infection, bleeding reoperation, increased hospital length of stay (LOHS) and mortality. Magnesium has been identified as a potentially interesting compound with easy access and low toxicity. Hypomagnesemia has been observed frequently immediately after cardiac surgery. Both reduction of abnormal atomicity of atrial myocardium and prolongation of the atrial refractory period caused by administration of magnesium may prevent AF. The POMPAE trial will analyse the effectiveness of MgSO4 versus placebo (double blind randomized trial) in the prevention of POAF after cardiac surgery.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation New Onset
• Intervention / Treatment: Drug: Magnesium sulfate

Detailed Description

Post-operative atrial fibrillation (POAF) is commonly observed in patients post cardiac surgery without a previous history of atrial fibrillation (AF) or other arrythmias. (1) Within this population, AF is considered to be multifactorial in origin (2) but associated with significant postoperative complications including infection, bleeding reoperation, increased hospital length of stay (LOHS) and mortality. (3,4) Multiple interventions have been tried before including anti-arrhythmic drugs (amiodaron, verapamil, sotalol) and rate reducing agents like beta-blockers. (5-7) Although encouraging results have been found with different regimes, adaptation in clinical practice has been hampered by toxicity (amiodarone) and therapeutic index. Magnesium has been identified as a potentially interesting compound with easy access and low toxicity; besides, hypomagnesemia has been observed frequently immediately after cardiac surgery. (8,9) Both reduction of abnormal activity of atrial myocardium and prolongation of the atrial refractory period caused by administration of magnesium may prevent AF. (10) Magnesium metabolism has identified that less then 1% of the total magnesium content is intravascular and serum levels don't always correlate with intracellular concentrations. (11) Hypomagnesaemia is associated with increased ventricular tachycardia and atrial fibrillation which is likely caused by a reduction in membrane triphosphate (ATP) activity. This results in reduced membrane stabilization due to a reduction in intracellular potassium compared to extracellular concentrations thus increasing electrical excitability. (12) Also measuring the intracellular concentration is difficult and especially in a routine fashion as loading tests followed by 24 hour urine analysis (13) and energy-dispersive X-ray analysis are not available. (14) Administration of magnesium sulphate does however correlate to higher intracellular magnesium concentration compared to placebo. (14) Several studies in different populations have shown a reduction in arrhythmias post magnesium supplementation. (15) Previous studies suggest that magnesium administration after cardiac surgery is effective in reducing the incidence of AF. (16) However, uncertainty remains regarding optimal dose/blood levels, duration and method of magnesium administration. (17) In a recent study using a protocol for administration of magnesium aiming for blood levels between 1.5 and 2.0 mmol/L an absolute reduction of POAF of 15.1% (OR 0.49, 95% CI 0.27-0.92) was demonstrated. (18) Based on this study, we designed the POMPAE trial (Peri-Operative Magnesium infusion to Prevent Atrial fibrillation Evaluated). The POMPAE trial is a double blinded randomized clinical trial to investigate the efficacy of magnesium supplementation and the reduction of POAF.

• Study Type: Interventional
• Enrollment (Estimated): 530
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jeroen Ludikhuize, MD, PhD, MSc; Phone Number: 4303 +31702100000; Email: j.ludikhuize@hagaziekenhuis.nl
• Study Contact Backup: Name: Anne-Marthe van den heuvel, MSc; Phone Number: +31702100000; Email: a.vandenheuvel@hagaziekenhuis.nl

Study Locations

• Netherlands
  • South-Holland
    • The Hague, South-Holland, Netherlands, 2545 AA
      • Recruiting
      • Hagaziekenhuis
      • Contact: Jeroen Ludikhuize, MD, PhD, MSc; Phone Number: 4303 +31702100000; Email: j.ludikhuize@hagaziekenhuis.nl
      • Contact: Anne-Marthe van den heuvel, MSc; Phone Number: +31702100000; Email: a.vandenheuvel@hagaziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Elective cardiac surgery (valve surgery and/or CABG)
• 18 years and above
• Mentally competent

Exclusion Criteria:

• History of atrial fibrillation (AF) or atrial flutter.
• Concomitant rhythm associated procedures (MAZE (surgical ablation)/PVI (pulmonary vein isolation)).
• Pre-existing severe renal impairment (eGFR<30 ml/min).
• Pre-existing 3rd degree heart block without pacemaker presence.

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
Active Comparator: Magnesium Sulfate; Magnesium sulfate is the active compound and will be administered to achieve plasma serum level of magnesium between 1.5 and 2.0 mmol/L according to the study protocol.	Drug: Magnesium sulfate; Based on serum levels, bolus and or continuous administration is provided as dictated by study protocol.; Other Names: magnesium
Placebo Comparator: Ringers Lactate; Ringers Lactate is the comparator/placebo and will be administered according to the study protocol.	Drug: Magnesium sulfate; Based on serum levels, bolus and or continuous administration is provided as dictated by study protocol.; Other Names: magnesium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of new-onset postoperative atrial fibrillation (POAF)	New-onset POAF over a period of 5 minutes or longer	First seven postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day postoperative atrial fibrillation (POAF) post-surgery	The incidence of POAF in the first 28 days post surgery diagnosed with ECG	28 days post surgery
Duration of POAF and peak heart rate recorded	The duration of POAF as recorded in the patient chart including the peak heart rate (in bpm)	28 days post surgery
Length of hospital stay	The total length of hospital stay from day of admission until hospital discharge irrespective of outcome (diseased, home, rehab etc)	Total duration of hospital stay
Length of ICU stay	The total length of ICU stay from the moment post surgery until discharge to the ward. Possible readmissions are not part of this outcome parameter	Total length of ICU stay after surgery
Duration of mechanical ventilation	The total length of invasive mechanical ventilation from the moment post surgery until discharge to the ward. Possible readmissions are not part of this outcome parameter	Total length of mechanical ventilation during ICU stay after surgery
Duration of inotropic and/or vasopressor support	The duration of inotropic and/or vasopressor support from the start of anaesthesia until discharge to the ward. Possible readmissions are not part of this outcome parameter	Total length of inotropic/vasopressor support from induction of anaesthesia until ICU discharge
Combined outcome including 28-day post-surgery mortality, stroke, pulmonary embolism, delirium (requiring any form of anti-psychotic medication and/or infection requiring antibiotics	The incidence of the combined outcome of 28-day mortality (outcome 2), the incidence of stroke as per advise neurology department, pulmonary embolism (Ct diagnosis), delirium requiring antipsychotics and/or the use of antibiotics apart from surgical/ICU prophylaxis.	28 days post surgery

Collaborators and Investigators

• Sponsor: HagaZiekenhuis
• Investigators: Principal Investigator: Jeroen Ludikhuize, MD, PhD, Medical specialist

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): December 30, 2022

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 7, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cardiac surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; 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: T-21-118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If required and request is made, this will be discussed within the study group and shared if no concerns are raised.
• IPD Sharing Time Frame: 2023/2024, a study protocol will be prepared as a separate manuscript and submitted for publication in a peer reviewed journal. This will also include the Statistical Analysis Plan.
• IPD Sharing Access Criteria: Upon acceptance of the study protocol in a peer reviewed journal, the materials are available online.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

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