{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T17:19:59Z","timestamp":1778260799016,"version":"3.51.4"},"reference-count":21,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"unspecified","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001065","name":"Australian Diabetes Society","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["107026"],"award-info":[{"award-number":["107026"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St Vincent\u2019s Clinic Foundation, Sydney, Australia","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,2,27]]},"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cardiac transplantation (CTx) is a life-saving operation that can improve the quality and length of a recipient\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u20138 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by St Vincent\u2019s Hospital Human Research Ethics Committee (2021\/ETH12184). The findings will be presented at national and international scientific meetings and published in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ACTRN12622000978763.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-069641","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T13:28:52Z","timestamp":1680096532000},"page":"e069641","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["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"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7048-2955","authenticated-orcid":false,"given":"Lisa Mary","family":"Raven","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia"},{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassia","family":"Kessler Iglesias","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole K","family":"Bart","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavitha","family":"Muthiah","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Kotlyar","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Macdonald","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher S","family":"Hayward","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Jabbour","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Heart and Lung Transplantation, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry R","family":"Greenfield","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia"},{"name":"Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia"},{"name":"School of Clinical Medicine, St Vincent\u2019s Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"2025120523474789000_13.3.e069641.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.07.015"},{"key":"2025120523474789000_13.3.e069641.2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011400604"},{"key":"2025120523474789000_13.3.e069641.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"2025120523474789000_13.3.e069641.4","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.120.052186"},{"key":"2025120523474789000_13.3.e069641.5","doi-asserted-by":"crossref","unstructured":"Liang B , Li R , Zhang P , et al . Empagliflozin for patients with heart failure and type 2 diabetes mellitus: clinical evidence in comparison with other sodium-glucose co-transporter-2 inhibitors and potential mechanism. J Cardiovasc Transl Res 15, 2022. doi:10.1007\/s12265-022-10302-4","DOI":"10.1007\/s12265-022-10302-4"},{"key":"2025120523474789000_13.3.e069641.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"2025120523474789000_13.3.e069641.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"2025120523474789000_13.3.e069641.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107038"},{"key":"2025120523474789000_13.3.e069641.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.008"},{"key":"2025120523474789000_13.3.e069641.10","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12850"},{"key":"2025120523474789000_13.3.e069641.11","doi-asserted-by":"crossref","first-page":"S284","DOI":"10.1016\/j.healun.2020.01.627","article-title":"Post-heart transplant diabetes mellitus: incidence, prevalence and outcomes","volume":"39","author":"Mazzone","year":"2020","journal-title":"The Journal of Heart and Lung Transplantation"},{"key":"2025120523474789000_13.3.e069641.12","first-page":"806","article-title":"New-onset diabetes mellitus after heart transplantation- incidence","volume":"81","author":"Kim","year":"2017","journal-title":"Risk Factors and Impact on Clinical Outcome Circ J"},{"key":"2025120523474789000_13.3.e069641.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.08.003"},{"key":"2025120523474789000_13.3.e069641.14","doi-asserted-by":"crossref","DOI":"10.1097\/TXD.0000000000000885","article-title":"Efficacy and safety of empagliflozin in the management of diabetes mellitus in heart transplant recipients","volume":"5","author":"Cehic","year":"2019","journal-title":"Transplant Direct"},{"key":"2025120523474789000_13.3.e069641.15","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.healun.2017.05.005","article-title":"Empagliflozin in the management of diabetes mellitus after cardiac transplantationresearch correspondenceretain-->","volume":"36","author":"Muir","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"2025120523474789000_13.3.e069641.16","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0093"},{"key":"2025120523474789000_13.3.e069641.17","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1111\/ajt.15223","article-title":"Empagliflozin in posttransplantation diabetes mellitus: a prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety","volume":"19","author":"Schwaiger","year":"2019","journal-title":"Am J Transplant"},{"key":"2025120523474789000_13.3.e069641.18","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1111\/ajt.14316","article-title":"Effect of empagliflozin on tacrolimus-induced pancreas islet dysfunction and renal injury","volume":"17","author":"Jin","year":"2017","journal-title":"Am J Transplant"},{"key":"2025120523474789000_13.3.e069641.19","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.healun.2020.06.007","article-title":"The cardioprotective potential of the sodium-glucose cotransporter 2 inhibitor empagliflozin in donor heart preservation","volume":"39","author":"Villanueva","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"2025120523474789000_13.3.e069641.20","doi-asserted-by":"crossref","first-page":"734","DOI":"10.4236\/jbise.2011.411090","article-title":"Implementation of an open-source customizable minimization program for allocation of patients to parallel groups in clinical trials","volume":"04","author":"Saghaei","year":"2011","journal-title":"JBiSE"},{"key":"2025120523474789000_13.3.e069641.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-069641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:48:01Z","timestamp":1765007281000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-069641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,29]]},"published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1136\/bmjopen-2022-069641"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-069641","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3]]}}}