EValuating the Effect of periopeRaTIve empaGliflOzin on cardiac surgery associated acute kidney injury: rationale and design of the VERTIGO Study

Abstract

Background Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication in patients undergoing cardiac surgery with extracorporeal circulation (ECC) that increases postoperative complications and mortality. CSA-AKI develops due to a combination of patient- and surgery-related risk factors that enhance renal ischemia-reperfusion injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin reduce renal glucose reabsorption, improving tubulo-glomerular feedback, reducing inflammation, and decreasing intraglomerular pressure. Preclinical studies have observed that SGLT2i may provide significant protection against renal ischemia-reperfusion injury due to its effects over inadequate mitochondrial function, reactive oxygen species activity, or renal peritubular capillary congestion, all hallmarks of CSA-AKI. The VERTIGO trial is a Phase 3, investigator-initiated, randomized, double-blind, placebo-controlled, multicenter study that aims to explore if empagliflozin can reduce the incidence of adverse renal outcomes in cardiac surgery patients. Methods The VERTIGO study (EudraCT: 2021–004938-11) will enroll 608 patients that require elective cardiac surgery with ECC. Patients will be randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg orally daily or placebo. Study treatment will start five days before surgery and will continue during the first seven postoperative days. All participants will receive standard care according to local practice guidelines. The primary endpoint of the study will be the proportion of patients that develop major adverse kidney events during the first 90 days after surgery, defined as 25% or greater renal function decline, renal replacement therapy initiation, or death. Secondary, tertiary, and safety endpoints will include rates of acute kidney injury during index hospitalization, postoperative complications, and observed adverse events. Conclusions The VERTIGO trial will describe the efficacy and safety of empagliflozin in preventing CSA-AKI. Patient recruitment is expected to start in May 2024.