Efficacy of Dapagliflozin in Reducing Postoperative Atrial Fibrillation and Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Grafting

The primary objective of the study is to establish the efficacy of **dapagliflozin** in reducing the incidence of new onset post-operative atrial fibrillation (AF) during hospitalization following coronary artery bypass graft (CABG) surgery. This is clinically relevant as post-operative AF is a common complication after CABG, leading to increased morbidity, prolonged hospital stays, and higher healthcare costs.

Secondary objectives include:

• Monitoring acute kidney injury (AKI) post-CABG, defined by specific changes in serum creatinine or urine output.
• Assessing the safety and tolerability of dapagliflozin, including adverse events (AEs), serious adverse events (SAEs), and suspected unexpected serious adverse reactions (SUSARs).
• Evaluating other in-hospital outcomes such as all-cause mortality, stroke, new onset heart failure, ventricular arrhythmia, and interventions for atrial fibrillation (AF) like electrical cardioversion and use of amiodarone.
• Measuring changes in inflammatory and cardiac biomarkers, as well as HbA1c levels, from baseline to three days post-CABG.
• Determining the length of intensive care unit and hospital stay.
• Post-discharge endpoints include 30-day and 12-month all-cause mortality, 12-month myocardial infarction, stroke, hospital admission for AF or heart failure, and dialysis treatment.

The clinical trial focuses on evaluating the efficacy of **dapagliflozin** in reducing the incidence of new onset post-operative atrial fibrillation during hospitalization following coronary artery bypass surgery (CABG). The study population includes both male and female participants aged 18 years and older, who are scheduled for CABG surgery with extracorporeal circulation. This may include patients undergoing additional procedures such as aortic valve replacement, mitral valve replacement or repair, or aortic root surgery, all with extracorporeal circulation. Participants are selected based on their diagnosis of chronic coronary syndrome, as documented by coronary angiography. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of **dapagliflozin** in reducing the incidence of new onset post-operative atrial fibrillation (AF) during hospitalization following coronary artery bypass graft (CABG) surgery. This study is a randomized, double-blind, controlled trial involving the administration of Forxiga 10 mg film-coated tablets and a placebo. The trial is expected to commence recruitment on February 1, 2024, and conclude by March 31, 2028. Participants will be randomly assigned to receive either the active treatment or placebo, with both groups undergoing identical procedures to ensure blinding.

The trial will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the **screening** visit, eligibility will be confirmed based on criteria such as age (≥18 years) and scheduled CABG surgery with extracorporeal circulation. Follow-up visits will occur during hospitalization to monitor the primary endpoint, which is the occurrence of AF lasting at least 30 seconds as detected on ECG or telemetry. Secondary endpoints include the incidence of acute kidney injury (AKI), safety and tolerability of dapagliflozin, and various other clinical outcomes such as all-cause mortality and stroke. The end-of-study visit will assess the overall health status of participants and collect final data.

Participant involvement is expected to last from the time of surgery until one week post-discharge, with additional follow-up for up to 12 months to monitor long-term outcomes. Conditions that may lead to early termination from the study include withdrawal of consent, significant adverse events, or any medical condition that contraindicates continued participation. The trial aims to provide robust data on the potential benefits of dapagliflozin in this specific surgical context, contributing to improved post-operative care for patients undergoing CABG surgery.

The clinical trial involves the administration of **Forxiga** 10 mg film-coated tablets, which contain the active substance **dapagliflozin**. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 240 mg over the course of the study. The treatment period is set for a maximum of 24 weeks. The tablets have been repackaged with new labels to facilitate a double-blind study design. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental medication, a **placebo** tablet is used as a comparator in this study. The placebo is designed to match the appearance of the Forxiga tablets to maintain the integrity of the double-blind study. The placebo is administered orally, following the same dosing schedule as the active treatment, to ensure consistency in the administration process. The placebo serves as a control to evaluate the efficacy of dapagliflozin in reducing the incidence of new onset post-operative atrial fibrillation during hospitalization following coronary artery bypass graft surgery.

The efficacy of dapagliflozin in the STENOTYPE trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the incidence of new onset **atrial fibrillation (AF)** lasting at least 30 seconds, as detected on ECG or telemetry, during hospitalization following coronary artery bypass graft (CABG) surgery. Secondary endpoints include the occurrence of acute kidney injury (AKI), defined by specific changes in serum creatinine levels or urine output, and monitored in-hospital post-CABG. Additional secondary endpoints encompass safety and tolerability of dapagliflozin, with adverse events (AEs), serious adverse events (SAEs), and suspected unexpected serious adverse reactions (SUSARs) being reported from the start of treatment until one week post-discharge. Other secondary measures include all-cause mortality, stroke, new onset heart failure, ventricular arrhythmia, and the use of amiodarone for AF. Changes in inflammatory and cardiac biomarkers will be evaluated from baseline to various timepoints post-CABG, including 6±2 hours, 12±2 hours, and three days after surgery. The trial will also assess changes in HbA1c levels, length of intensive care unit and hospital stay, and mortality and morbidity outcomes at 30 days and 12 months post-surgery.