Department of Diabetes and Endocrinology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia
Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
BMJ Open. 2023 Mar 29;13(3):e069641. doi: 10.1136/bmjopen-2022-069641.
Cardiac 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.
The 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.
This 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.
ACTRN12622000978763.
心脏移植（CTx）是一种挽救生命的手术，可以提高受者的生活质量和延长寿命。为了预防排斥反应，需要使用免疫抑制药物，但这可能会导致代谢和肾脏不良影响。临床上显著的并发症包括代谢影响，如糖尿病和体重增加、肾功能损害以及移植物血管病和心肌纤维化等心脏疾病。钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂是一类可增加尿葡萄糖排泄的口服药物。在 2 型糖尿病患者中，SGLT2 抑制剂可改善心血管、代谢和肾脏结局。无论糖尿病状态如何，在射血分数降低的心力衰竭患者中，也观察到了类似的益处。在移植后糖尿病患者中，SGLT2 抑制剂可改善代谢参数；然而，其在随机前瞻性研究中的获益和安全性尚未得到评估。本研究可能为改善或预防免疫抑制药物引起的并发症（糖尿病、肾功能衰竭和心脏纤维化）提供一种新的治疗方法。
EMPA-HTx 研究是一项 SGLT2 抑制剂恩格列净 10mg 每日治疗与安慰剂在近期 CTx 受者中的随机、安慰剂对照试验。100 名参与者将按照 1:1 随机分组，并在移植后 6-8 周内开始研究药物治疗，随访至移植后 12 个月。在基线和随访时记录人口统计学信息、人体测量学测量、病理学检查和心脏磁共振（CMR）扫描。在研究期间，患者每月进行一次检查，直到 CTx 后 12 个月，并在每次研究就诊时收集每位患者的数据。该研究的总体目的是评估恩格列净在 CTx 受者中的安全性和疗效。主要结局是糖化血红蛋白和/或果糖胺的变化来衡量血糖改善情况。关键次要结局是通过 CMR 测量的心脏间质纤维化和通过估计肾小球滤过率测量的肾功能。
本研究已获得圣文森特医院人类研究伦理委员会（2021/ETH12184）的批准。研究结果将在国内和国际科学会议上进行报告，并发表在同行评议的期刊上。
ACTRN12622000978763。
