Sodium glucose co-transporter 2 inhibition with empagliflozin on metabolic, cardiac and renal outcomes in recent cardiac transplant recipients (EMPA-HTx): protocol for a randomised controlled trial

Abstract

IntroductionCardiac transplantation (CTx) is a life-saving operation that can improve the quality and length of a recipient’s life. Immunosuppression medication, required to prevent rejection, can result in adverse metabolic and renal effects. Clinically significant complications include metabolic effects such as diabetes and weight gain, renal impairment, and cardiac disease such as allograft vasculopathy and myocardial fibrosis. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of oral medication that increase urinary excretion of glucose. In patients with type 2 diabetes, SGLT2 inhibitors improve cardiovascular, metabolic and renal outcomes. Similar benefits have been shown in patients with heart failure and reduced ejection fraction irrespective of diabetes status. In patients with post-transplant diabetes mellitus, SGLT2 inhibitors improve metabolic parameters; however, their benefit and safety have not been evaluated in randomised prospective studies. This study will potentially provide a novel therapy to improve or prevent complications (diabetes, kidney failure and heart fibrosis) that occur with immunosuppressive medications.MethodsThe EMPA-HTx study is a randomised, placebo-controlled trial of the SGLT2 inhibitor empagliflozin 10 mg daily versus placebo in recent CTx recipients. One hundred participants will be randomised 1:1 and commence the study medication within 6–8 weeks of transplantation with treatment and follow-up until 12 months after transplantation. Demographic information, anthropomorphic measurements, pathology tests and cardiac magnetic resonance (CMR) scan will be recorded at baseline and follow-up. Patients will be reviewed monthly during the study until 12 months post-CTx and data will be collected for each patient at each study visit. The overall aim of the study is to assess the safety and efficacy of empagliflozin in CTx recipients. The primary outcome is glycaemic improvement measured as change in glycated haemoglobin and/or fructosamine. Key secondary outcomes are cardiac interstitial fibrosis measured by CMR and renal function measured by estimated glomerular filtration rate.Ethics and disseminationThis study has been approved by St Vincent’s Hospital Human Research Ethics Committee (2021/ETH12184). The findings will be presented at national and international scientific meetings and published in peer-reviewed journals.Trial registration numberACTRN12622000978763.

Kidneys in heart failure: Impact of flozins

“…SGLT2i, though well-established in the treatment of diabetes, CVD, and CKD (and any combination of these diseases) and included in many national and international guidelines are still the subject of clinical research -new trials are planned or ongoing to make indications to SGLT2i even broader. The key directions of such research include use of SGLT2i in heart transplant and kidney transplant recipients, acute heart failure, coronary artery disease and acute myocardial infarction, or treatment of diseases contributing to increased risk of CVD and CKD, such as sleep apnea syndrome [91][92][93][94][95][96]. Randomized trials are also planned or ongoing that assess the efficacy of SGLT2i combined with another drug with confirmed cardiovascular and renal benefits in T2DM patients, namely finerenone, a onein-the-class non-steroidal mineral corticosteroid receptor antagonist [97].…”