Clinical trial NCT05669417: Peri-Operative Magnesium Infusion to Prevent Atrial Fibrillation Evaluated.
Official title: Randomized Controlled Trial of Magnesium Sulfate Versus Placebo on the Prevention of Atrial Fibrillation Post Cardiac Surgery.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Atrial Fibrillation New Onset
Keywords: Cardiac surgery
Lead sponsor: HagaZiekenhuis
Sponsor class: OTHER
First posted: 2022-12-30
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded RCT
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Incidence of new-onset postoperative atrial fibrillation (POAF)
timeFrame: First seven postoperative days
Secondary outcomes:
measure: 28-day postoperative atrial fibrillation (POAF) post-surgery
timeFrame: 28 days post surgery
measure: Duration of POAF and peak heart rate recorded
timeFrame: 28 days post surgery
measure: Length of hospital stay
timeFrame: Total duration of hospital stay
measure: Length of ICU stay
timeFrame: Total length of ICU stay after surgery
measure: Duration of mechanical ventilation
timeFrame: Total length of mechanical ventilation during ICU stay after surgery
measure: Duration of inotropic and/or vasopressor support
timeFrame: Total length of inotropic/vasopressor support from induction of anaesthesia until ICU discharge
measure: Combined outcome including 28-day post-surgery mortality, stroke, pulmonary embolism, delirium (requiring any form of anti-psychotic medication and/or infection requiring antibiotics
timeFrame: 28 days post surgery
Other outcomes:
Locations:
city: The Hague
country: Netherlands
facility: HagaZiekenhuis
state: South-Holland
Study officials:
affiliation: Medical specialist
name: Jeroen Ludikhuize, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: