THU298 Effect Of SGLT2 Inhibition On Metabolic, Cardiac And Renal Outcomes In Heart Transplant Recipients (EMPA-HTx study): Protocol And Study Design

Disclosure: L.M. Raven: None. C.A. Muir: None. C. Kessler Iglesias: None. E. Kotlyar: None. K. Muthiah: None. N.K. Bart: Advisory Board Member; Self; Bristol-Myers Squibb. Grant Recipient; Self; Pfizer, Inc. Speaker; Self; Pfizer, Inc. P.S. Macdonald: Speaker; Self; Boehringer Ingelheim, AstraZeneca. C.S. Hayward: None. A. Jabbour: None. J.R. Greenfield: Speaker; Self; Boehringer Ingelheim, AstraZeneca. Background: Heart transplantation (HTx) is standard of care for treatment of end-stage heart failure. Immunosuppression medication, required to prevent rejection, can result in adverse metabolic and renal effects. Clinically significant post-transplant complications include metabolic (diabetes, weight gain), renal impairment and cardiac disease, such as allograft vasculopathy and myocardial fibrosis. Sodium glucose co-transporter 2 inhibitors (SGLT2i) may have positive effects on all of these post-transplant complications. SGLT2i have been observed to improve metabolic parameters in patients with type 2 diabetes following cardiac and renal transplantation, but their benefit and safety in HTx has not been evaluated in randomised prospective studies. Aims: The overall aim of this project is to study the safety and efficacy of empagliflozin in HTx recipients. The primary end point will be improvement in glycaemic control assessed by change in glycosylated hemoglobin (HbA1c) and/or fructosamine, with secondary endpoints of cardiac fibrosis assessed by cardiac magnetic resonance, and renal function assessed by serum creatinine. Methods: Randomised, placebo-controlled trial of empagliflozin 10 mg daily versus placebo in recent HTx recipients. One hundred participants will be randomised 1:1. They will commence the study medication within 6-8 weeks of transplantation. Follow up will be 12 months after transplantation. Results from routine pre-HTx assessment will be reviewed to assess for pre-HTx diagnosis of diabetes. Routine laboratory tests, including full blood count, biochemistry, glucose, lipids and liver function as well as HbA1c, fructosamine, beta-hydroxybutyrate and urine albumin creatinine ratio, will be measured at baseline prior to receipt of study drug or placebo. Patients will be reviewed monthly during the study until 12 months post-HTx and data will be collected for each patient at each study visit. Cardiovascular magnetic resonance will be measured at baseline and 12 months after HTx. This study has been approved by St Vincent’s Hospital Human Research Ethics Committee (2021/ETH12184). Trial registration: ACTRN12622000978763. Discussion: This study will, for the first time, determine the efficacy and safety of SGLT2i in HTx recipients. Presentation: Thursday, June 15, 2023