Peri-Operative Magnesium Infusion to Prevent Atrial Fibrillation Evaluated.

Atrial Fibrillation New Onset Clinical Trial

— POMPAE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05669417
• Other study ID #: T-21-118
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 1, 2022
• Est. completion date: January 31, 2025

Study information

• Verified date: January 2024
• Source: HagaZiekenhuis
• Contact: Jeroen Ludikhuize, MD, PhD, MSc
• Phone: +31702100000
• Email: j.ludikhuize[@]hagaziekenhuis.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 530
• Est. completion date: January 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation New Onset

Intervention

Drug:
• Magnesium sulfate
Based on serum levels, bolus and or continuous administration is provided as dictated by study protocol.

Locations

Country	Name	City	State
Netherlands	HagaZiekenhuis	The Hague	South-Holland

Sponsors (1)

Lead Sponsor	Collaborator
HagaZiekenhuis

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of new-onset postoperative atrial fibrillation (POAF)	New-onset POAF over a period of 5 minutes or longer	First seven postoperative days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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