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

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

doi:10.1002/ehf2.12366

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

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

^*Corresponding author for this work

Department of Clinical Medicine

12 Citations (Scopus)

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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.

Original language	English
Journal	ESC heart failure
Volume	6
Issue number	1
Pages (from-to)	174-181
Number of pages	8
ISSN	2055-5822
DOIs	https://doi.org/10.1002/ehf2.12366
Publication status	Published - Feb 2019

Keywords

Advanced heart failure
Global rank endpoint
Hospitalization
Levosimendan
N-terminal pro-brain natriuretic peptide
Randomized controlled trial

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10.1002/ehf2.12366Licence: CC BY-NC-ND

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post‐discharge periodFinal published version, 314 KBLicence: CC BY-NC-ND

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Pölzl, G., Allipour Birgani, S., Comín-Colet, J., Delgado, J. F., Fedele, F., García-Gonzáles, M. J., Gustafsson, F., Masip, J., Papp, Z., Störk, S., Ulmer, H., Vrtovec, B., Wikström, G., & Altenberger, J. (2019). Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period. ESC heart failure, 6(1), 174-181. https://doi.org/10.1002/ehf2.12366

Pölzl, G, Allipour Birgani, S, Comín-Colet, J, Delgado, JF, Fedele, F, García-Gonzáles, MJ, Gustafsson, F, Masip, J, Papp, Z, Störk, S, Ulmer, H, Vrtovec, B, Wikström, G & Altenberger, J 2019, 'Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period', ESC heart failure, vol. 6, no. 1, pp. 174-181. https://doi.org/10.1002/ehf2.12366

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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.",

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AU - Pölzl, Gerhard

AU - Allipour Birgani, Shadab

AU - Comín-Colet, Josep

AU - Delgado, Juan F.

AU - Fedele, Francesco

AU - García-Gonzáles, Martín Jesús

AU - Gustafsson, Finn

AU - Masip, Josep

AU - Papp, Zoltán

AU - Störk, Stefan

AU - Ulmer, Hanno

AU - Vrtovec, Bojan

AU - Wikström, Gerhard

AU - Altenberger, Johann

PY - 2019/2

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N2 - 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.

AB - 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.

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KW - Hospitalization

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KW - N-terminal pro-brain natriuretic peptide

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DO - 10.1002/ehf2.12366

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EP - 181

JO - ESC heart failure

JF - ESC heart failure

IS - 1

ER -

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

Abstract

Keywords

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