Empagliflozin to Prevent Post-Operative Atrial Fibrillation (EMPOAF)

Evaluating the Role of EMpagliflozin on the Rate of Post-Operative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Graft Surgery: a Double-blind Placebo-controlled Randomized Clinical Trial

This is an interventional, double-blind, placebo controlled, multicenter, randomized clinical trial with allocation sequence concealment and blinded endpoint adjudication. The goal of present study is to investigate if periprocedural administration of 10 mg once daily empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2I), can reduce the incidence of post-operative atrial fibrillation and/or atrial flutter in patients with chronic coronary syndrome scheduled for isolated CABG. This trial will be conducted in two referral teaching cardiology hospitals in Tehran. 492 adult patients who are scheduled for elective isolated coronary artery bypass graft (CABG) surgery will be randomly assigned to one of the groups of intervention (empagliflozin 10 mg daily) or placebo starting 3 days before surgery until discharge.

Study Overview

• Status: Recruiting
• Conditions: CABG; Post-operative Atrial Fibrillation
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Placebo

Detailed Description

Study aim: Evaluating the role of empagliflozin on the rate of postoperative atrial fibrillation in comparison with placebo Design: Two arms, parallel-group, phase 3, randomized, double-blind, placebo-controlled trial on 492 patients Settings and conduct: Recruitment site: Tehran Heart Center and Rajaie Cardiovascular Medical and Research Center For blinding, the drug or placebo will be given to the ward based on the patient's code in the randomization system For monitoring, the blood samples for creatinine, sodium, potassium, and fasting blood sugar along with clinical evaluations will be given on day 0 and daily thereafter (max= 30 days) in specific wards and will be compared at the end of any atrial fibrillation lasting longer than 30 seconds based on 24-hour 12-lead ECG monitoring will be accepted as atrial fibrillation After entering the study, the patients are placed in one of two groups, sample and control; in the sample group, they are treated with the usual treatment regimen plus empagliflozin at a dose of 10 mg during the hospitalization period. Patients in the control arm will receive a matching placebo.

• Study Type: Interventional
• Enrollment (Estimated): 492
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hessam Kakavand, PharmD; Phone Number: +982144605351; Email: hessamkakavand@yahoo.com
• Study Contact Backup: Name: Maryam Aghakouchakzadeh, PharmD; Phone Number: +982188029600; Email: m.aghakouchakzadeh@gmail.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1411713138
    • Recruiting
    • Tehran Heart Center
    • Contact: Maryam Aghakouchakzadeh, PharmD; Phone Number: +982188029600; Email: m.aghakouchakzadeh@gmail.com
  • Tehran, Iran, Islamic Republic of, 1995614331
    • Recruiting
    • Rajaie Cardiovascular Medical & Research Center
    • Contact: Hessam Kakavand, PharmD; Phone Number: +98 21 23921; Email: hessamkakavand@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Adult patients (≥18 years) who are candidates for isolated CABG
• Patients who provided written informed consent and are willing to participate in the study

Exclusion criteria

• History of type Ⅰ or Ⅱ diabetes mellitus
• History of ketoacidosis
• History of atrial fibrillation or flutter
• History of recurrent UTI
• SGLT2I or any other oral hypoglycemic medications used due to other indications
• Patients with acute kidney injury (45)
• Severe hepatic disease (Child-Pugh score C)
• Patients with Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73m2
• Patients who are candidates for emergent CABG
• Patients with unstable hemodynamic state
• Patients with positive urine culture, urinary symptoms (frequency, dysuria, hesitancy), and asymptomatic bacteriuria
• Patients who are enrolled in other clinical trials
• Patients with a history of drug-sensitive reactions to SGLT2I
• Pregnancy or lactation

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: Intervention group; The intervention group will receive a 10 mg tablet of empagliflozin once a day from 3 days before surgery until discharge from the hospital.	Drug: Empagliflozin 10 MG; The intervention group will receive a 10 mg tablet of empagliflozin once a day from 3 days before surgery until discharge from the hospital.
Placebo Comparator: Comperator; The comparator group will receive a matching placebo	Drug: Placebo; The comparator group will receive a matching placebo from 3 days before surgery until discharge from the hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of POAF	Incidence of new-onset postoperative atrial fibrillation (AF) and/or atrial flutter (AFL), defined as any adjudicated documented AF or AFL of at least 30 seconds duration and documented by Holter ECG monitoring during the admission time in the ICU (at least 72 hours and maximum 30 days).	From CABG until discharge from the intensive care unit (at least 72 hours and maximum 30 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Incidence of all arrhythmias leading to hemodynamic instability	Defined as any adjudicated documented tachy- or bradyarrhythmia of at least 30 seconds duration and documented by rhythm strips or 12-lead ECG leading to hemodynamic instability during the admission time. Ventricular tachycardia (VT) of at least 30 seconds duration and documented by rhythm strip or 12-lead ECG. Ventricular fibrillation (VF) of at least 30 seconds duration and documented by rhythm strip or 12-lead ECG	From CABG until discharge from the hospital (maximum 30 days).
Incidence of post-operative acute kidney injury	Defined as the presence of either the increase in serum creatinine by ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours; or an increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine volume < 0.5 ml/kg/h for 6 hours based on the KDIGO definition of AKI	From CABG until 7th post-operation day.
Need for vasopressor/inotrope	Defined as cumulative vasopressor index and the amount of average daily inotrope dose during the admission time in the ICU	From CABG until discharge from the intensive care unit (maximum 30 days).
Duration of hospitalization	Defined as number of days a patient stay at the hospital	From CABG until discharge from the hospital.
All-cause mortality	Defined as adjudicated 30-day mortality, including cause-specific mortality: cardiac arrhythmic, cardiac non-arrhythmic, and non-cardiovascular.	From CABG until 30th post-operation day.
Incidence of life-threatening infections	Defined as any adjudicated laboratory and clinically confirmed systemic infection that necessitate the administration of parenteral broad spectrum antibiotics	From CABG until discharge (maximum 30 days).
Incidence of genitourinary tract infections	Defined as any adjudicated laboratory and clinically confirmed genitourinary tract infection including cystitis, pyelonephritis, prostatitis, urethritis, and vaginitis	From CABG until discharge from the hospital (maximum 30 days).
Incidence of hypoglycemia	Defined as serum blood sugar ≤ 70 mg/dL (≤ 3.9 mmol/L)	From CABG until discharge from the hospital (maximum 30 days).
Incidence of ketoacidosis	Defined as blood pH ≤ 7.3, serum bicarbonate less than 15 mEq/l, and presence of ketonemia or ketonuria	From CABG until discharge from the hospital (maximum 30 days).
Incidence of clinically-diagnosed ischemic stroke	Defined as the sudden loss of blood circulation to an area of the brain that has been confirmed with appropriate diagnostic imaging (Brain CT/MRI)	From CABG until 30th post-operation day.
Composite incidence of arterial and venous thrombosis	Defined as adjudicated arterial thrombosis (including Type I MI and peripheral arterial thrombosis) and venous thrombosis (including DVT and PE) confirmed with appropriate diagnostic tools	From CABG until 30th post-operation day.
Need for renal replacement therapy	defined as treatment with any forms of dialysis (hemodialysis, hemodiafiltration, and peritoneal dialysis), hemofiltration, and renal transplantation	From CABG until discharge from the intensive care unit (maximum 30 days).

Collaborators and Investigators

• Sponsor: Rajaie Cardiovascular Medical and Research Center
• Collaborators: Tehran Heart Center

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: November 6, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; CABG; Empagliflozin; SGLT2 inhibitors; Cardiac surgery; Post-operative AF
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: IRCT20230110057098N1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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