Peri-Operative Magnesium Infusion to Prevent Atrial Fibrillation Evaluated.

NCT ID: NCT05669417

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2023-08-06

Brief Summary

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.

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.

Conditions

Atrial Fibrillation New Onset

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Magnesium sulfate

Intervention Type: DRUG

Based on serum levels, bolus and or continuous administration is provided as dictated by study protocol.

Ringers Lactate

Ringers Lactate is the comparator/placebo and will be administered according to the study protocol.

Group Type: PLACEBO_COMPARATOR

Magnesium sulfate

Intervention Type: DRUG

Based on serum levels, bolus and or continuous administration is provided as dictated by study protocol.

Interventions

Magnesium sulfate

Based on serum levels, bolus and or continuous administration is provided as dictated by study protocol.

Intervention Type: DRUG

Other Intervention Names

magnesium

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HagaZiekenhuis

OTHER

Sponsor Role: lead

Responsible Party

Jeroen Ludikhuize

MD, PhD, MSc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeroen Ludikhuize, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical specialist

Locations

HagaZiekenhuis

The Hague, South Holland, Netherlands

Countries

Netherlands

References

Meerman M, Buijser M, van den Berg L, van den Heuvel AM, Hoohenkerk G, van Driel V, Munsterman L, de Vroege R, Bailey M, Bellomo R, Ludikhuize J. Magnesium sulphate to prevent perioperative atrial fibrillation in cardiac surgery: a randomized clinical trial : A protocol description of the PeriOperative Magnesium Infusion to Prevent Atrial fibrillation Evaluated (POMPAE) trial. Trials. 2024 Aug 15;25(1):540. doi: 10.1186/s13063-024-08368-3.

Reference Type: DERIVED

PMID: 39148128 (View on PubMed)

Other Identifiers

T-21-118

Identifier Type: -

Identifier Source: org_study_id