{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:17:38Z","timestamp":1771103858285,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":2638,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T00:00:00Z","timestamp":1540857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Orion Pharma"},{"name":"Orion Pharma"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks.<\/jats:p>","DOI":"10.1002\/ehf2.12366","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:11:26Z","timestamp":1540944686000},"page":"174-181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Repetitive Levosimendan Infusions for Patients with Advanced Chronic Heart Failure in the Vulnerable Post-Discharge Period"],"prefix":"10.1093","volume":"6","author":[{"given":"Gerhard","family":"P\u00f6lzl","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III, Medical University Innsbruck , Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shadab","family":"Allipour Birgani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Medical University Innsbruck , Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Com\u00edn-Colet","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Bellvitge University Hospital and IDIBELL, University of Barcelona Hospitalet de Llobregat , Barcelona ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan F.","family":"Delgado","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital 12 de Octubre, CIBERCV , Madrid ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Fedele","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome , Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mart\u00edn Jes\u00fas","family":"Garc\u00eda-Gonz\u00e1les","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Canarias , San Crist\u00f3bal de La Laguna, Tenerife ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital, Rigshospitalet , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Masip","sequence":"additional","affiliation":[{"name":"Intensive Care Department, Consorci Sanitari Integral, University of Barcelona , Barcelona ,","place":["Spain"]},{"name":"Cardiology Department, Hospital Sanitas CIMA , Barcelona ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Papp","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Clinical Physiology, Faculty of Medicine, University of Debrecen , Debrecen ,","place":["Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"St\u00f6rk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Comprehensive Heart Failure Center, University Hospital W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanno","family":"Ulmer","sequence":"additional","affiliation":[{"name":"Department for Medical Statistics, Informatics and Health Economics, Medical University Innsbruck , Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bojan","family":"Vrtovec","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Ljubljana , Ljubljana 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