Evaluation of Dapagliflozin for the Prevention of Acute Kidney Injury in Patients Undergoing Cardiac Surgery

The primary objective of the study titled "proMoting Effective Renoprotection in Cardiac sURgery patients by Inhibition of SGLT-2" (MERCURI-2) is to **prevent Acute Kidney Injury (AKI)** in patients undergoing cardiac surgery. This is clinically relevant as AKI is a common and serious complication in this patient population, leading to increased morbidity and mortality. The study evaluates the efficacy of **dapagliflozin**, administered as Forxiga 10 mg film-coated tablets, in achieving this objective. No secondary objectives are specified for this study.

The clinical trial focuses on the prevention of **acute kidney injury (AKI)** in patients undergoing elective cardiac surgery, specifically those involving cardio-pulmonary bypass (CPB) or off-pump coronary artery bypass surgery (OPCAB). The study population includes both male and female participants aged over 18 years. The trial does not involve a vulnerable population. Participants are required to provide informed consent. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of individuals who are scheduled for specific types of cardiac surgery, ensuring a targeted approach to the study's objective.

The clinical trial is designed to evaluate the efficacy of **dapagliflozin** in preventing acute kidney injury (AKI) in patients undergoing elective cardiac surgery. This is a randomized, double-blind, controlled trial, with participants receiving either the investigational product or a placebo. The trial is expected to last until June 2025, with recruitment having commenced in June 2023. Participants will be involved in the study for a maximum treatment period of six months, during which they will receive a daily dose of 10 mg of the investigational product, administered orally in the form of film-coated tablets.

The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits to monitor progress, and an end-of-study visit to assess outcomes. The inclusion criteria require participants to be over 18 years old, undergoing elective cardiac surgery with cardio-pulmonary bypass or off-pump coronary artery bypass surgery, and providing informed consent. The primary endpoint is the incidence of AKI within seven days post-surgery, as defined by KDIGO criteria. Secondary endpoints include the occurrence of stage 3 AKI, changes in estimated glomerular filtration rate (eGFR), and various postoperative complications and quality of recovery measures.

Participants may be withdrawn from the study if they experience serious adverse events or if they no longer meet the inclusion criteria. The trial will also assess safety outcomes, including the incidence of genital mycotic infections, diabetic ketoacidosis, and hypoglycemia. The study aims to provide comprehensive data on the effectiveness and safety of dapagliflozin in this new indication, contributing to the understanding of its potential benefits in cardiac surgery patients.

The clinical trial involves the administration of **Forxiga 10 mg film-coated tablets**, which contain the active substance **dapagliflozin**. Dapagliflozin is a chemical compound classified under the ATC code A10BK01. The pharmaceutical form of the medication is a film-coated tablet, designed for oral administration. Each tablet contains 10 mg of dapagliflozin. The maximum daily dose is 10 mg, with a total maximum dose of 60 mg over the course of the treatment. The treatment period is limited to a maximum of 6 months. For blinding purposes, the dapagliflozin tablets are over-encapsulated, and the capsules are backfilled with microcrystalline cellulose PH102. The medication is manufactured by AstraZeneca AB and is not a paediatric formulation.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial's main objective is to prevent acute kidney injury (AKI) in cardiac surgery patients through the inhibition of SGLT-2. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The administration of the medication is strictly oral, and the trial does not involve any additional devices or characteristics related to the drug administration.

Efficacy in the clinical trial titled "proMoting Effective Renoprotection in Cardiac sURgery patients by Inhibition of SGLT-2" will be assessed using both primary and secondary endpoints. The primary endpoint is the incidence of **Acute Kidney Injury (AKI)** within 7 days after surgery, evaluated according to the KDIGO criteria. Secondary endpoints include several measures: Stage 3 AKI as per KDIGO criteria, postoperative maximum change of estimated Glomerular Filtration Rate (eGFR) compared to baseline, and the occurrence of de novo postoperative atrial fibrillation as recorded on a 12-lead ECG. Additional secondary endpoints involve the length of stay in the Intensive Care Unit (LoS-ICU) and hospital (LoS-Hos), Major Adverse Kidney Events (MAKE), and Major Adverse Cardiovascular Events (MACE).

Patient-reported outcomes will be assessed using three questionnaires: DAH30, WHO-DAS 2.0, and EQ5D5L. Safety outcomes will include monitoring for genital mycotic infections, diabetic keto-acidosis, hypoglycemia, and other postoperative complications and Serious Adverse Events (SAEs). Healthcare and productivity costs will be evaluated using the iPCQ and IMCQ questionnaires. Peri-operative glucose measurements and hemodynamic vital signs will be routinely measured, alongside postoperative cardiac function assessments through echocardiography and cardiac biomarkers. Urine oxygenation will be measured with an oxygen sensor in the urinary catheter, tracking mean intraoperative and postoperative oxygenation levels and their correlation with AKI markers.