Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period.

Abstract

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.

• Authors: Gerhard Pölzl, Shadab Allipour Birgani, Josep Comín-Colet, Juan F Delgado, Francesco Fedele, Martín Jesús García-Gonzáles, Finn Gustafsson, Josep Masip, Zoltán Papp, Stefan Störk, Hanno Ulmer, Bojan Vrtovec, Gerhard Wikström, Johann Altenberger
• Journal: ESC heart failure (ESC Heart Fail) Vol. 6 Issue 1 Pg. 174-181 (02 2019) ISSN: 2055-5822 [Electronic] England
• PMID: 30378288 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Chemical References

• Cardiotonic Agents
• Simendan

Topics

• Cardiotonic Agents (administration & dosage)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Follow-Up Studies
• Heart Failure (drug therapy, physiopathology)
• Humans
• Infusions, Intravenous
• Patient Discharge
• Simendan (administration & dosage)
• Stroke Volume (physiology)
• Treatment Outcome