open access
Early administration of LEvosimendan in Patients witH decompensAted chroNic hearT failure (ELEPHANT) study. Rationale and protocol of the study
, 1, 2, 1, 3, 2, 1, 1, 1, 1, 1, 4, 1, 5, 2, 2, 1, 1, 6, 1, 1, 1, 1
Affiliations- Department of Cardiology and Internal Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz, Poland
- Department of Cardiac Rehabilitation and Health Promotion, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Poland
- 3Gajda-Med Medical Centre, Pultusk, Poland
- Department of Geriatrics, Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz, Poland
- Department of Pharmacology, Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz, Poland
- Department of Heath Economy, Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz, Poland
open access
Abstract
Dobutamine and levosimendan are both indicated for inotropic support in acute decompensated heart failure (HF).
The study aimed to assess the impact of early administration of levosimendan (first iv therapeutic approach) versus dobutamine (first iv therapeutic approach) on in-hospital treatment expenses and clinical outcomes in patients with decompensated chronic HF.
The ELEPHANT study was designed as a phase III, multicentre, randomized 1:1, double-blind, active-controlled trial that will include patients admitted to the hospital due to HF decompensation. Co-primary endpoints were defined as total in-hospital expenses/survivor and duration of hospitalization/survivor. Secondary efficacy endpoints: on the last day of hospitalization: occurrence of treatment side effects, body weight change during hospitalization, BNP change during hospitalization, in-hospital mortality, additional levosimendan administration due to the ineffectiveness of the initial treatment. Patients will be randomized 1:1 to the active group receiving continuous infusion 24 h of levosimendan 0.1 μg/kg/min or to the control group receiving continuous infusion 24 h of dobutamine 3 μg/kg/min.
After the enrolment of 20 patients, results analysis will be performed (pilot phase — single centre). Based on this analysis conducted according to the intention-to-treat principle, the final population size will be defined. The multicentre phase of the study will be initiated after the pilot phase.
Abstract
Dobutamine and levosimendan are both indicated for inotropic support in acute decompensated heart failure (HF).
The study aimed to assess the impact of early administration of levosimendan (first iv therapeutic approach) versus dobutamine (first iv therapeutic approach) on in-hospital treatment expenses and clinical outcomes in patients with decompensated chronic HF.
The ELEPHANT study was designed as a phase III, multicentre, randomized 1:1, double-blind, active-controlled trial that will include patients admitted to the hospital due to HF decompensation. Co-primary endpoints were defined as total in-hospital expenses/survivor and duration of hospitalization/survivor. Secondary efficacy endpoints: on the last day of hospitalization: occurrence of treatment side effects, body weight change during hospitalization, BNP change during hospitalization, in-hospital mortality, additional levosimendan administration due to the ineffectiveness of the initial treatment. Patients will be randomized 1:1 to the active group receiving continuous infusion 24 h of levosimendan 0.1 μg/kg/min or to the control group receiving continuous infusion 24 h of dobutamine 3 μg/kg/min.
After the enrolment of 20 patients, results analysis will be performed (pilot phase — single centre). Based on this analysis conducted according to the intention-to-treat principle, the final population size will be defined. The multicentre phase of the study will be initiated after the pilot phase.
Keywords
levosimendan, dobutamine, decompensated heart failure
About this articleTitle
Early administration of LEvosimendan in Patients witH decompensAted chroNic hearT failure (ELEPHANT) study. Rationale and protocol of the study
Journal
Issue
Article type
Original article
Pages
91-95
Published online
2023-05-10
Page views
1283
Article views/downloads
323
DOI
Bibliographic record
Medical Research Journal 2023;8(2):91-95.
Keywords
levosimendan
dobutamine
decompensated heart failure
Authors
Jacek Kubica
Krzysztof Pstrągowski
Aldona Kubica
Tomasz Topoliński
Robert Gajda
Łukasz Pietrzykowski
Ewa Zabielska
Tamara Sukiennik
Małgorzata Jasiewicz
Marzena Wawrzyniak
Malwina Barańska
Julia M. Umińska
Lidia Manelska
Ewa Obońska
Michał Siedlaczek
Piotr Michalski
Ewa Laskowska
Klaudyna Grzelakowska
Jacek Kryś
Piotr Adamski
Piotr Niezgoda
Małgorzata Ostrowska
Eliano P. Navarese
References (32)- McDonagh TA, Metra M, Adamo M, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42(36): 3599–3726.
- Kubica J. Heart failure treatment according to the 2021 European Society of Cardiology Guidelines — experiences with SGLT2 inhibitors have changed the treatment strategy. Medical Research Journal. 2021; 6(3): 163–165.
- Bayram M, De Luca L, Massie MB, et al. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005; 96(6A): 47G–58G.
- Delaney A, Bradford C, McCaffrey J, et al. Levosimendan for the treatment of acute severe heart failure: a meta-analysis of randomised controlled trials. Int J Cardiol. 2010; 138(3): 281–289.
- Pollesello P, Parissis J, Kivikko M, et al. Levosimendan meta-analyses: Is there a pattern in the effect on mortality? Int J Cardiol. 2016; 209: 77–83.
- Tycińska A, Gierlotka M, Bartuś S, et al. LEIA-HF Investigators. Repetitive use of LEvosimendan in Ambulatory Heart Failure patients (LEIA-HF) - The rationale and study design. Adv Med Sci. 2022; 67(1): 18–22.
- Jaguszewski MJ, Gasecka A, Targonski R, et al. Efficacy and safety of levosimendan and dobutamine in heart failure: A systematic review and meta-analysis. Cardiol J. 2021; 28(3): 492–493.
- Tycińska A, Gierlotka M, Bugajski J, et al. Levosimendan in the treatment of patients with acute cardiac conditions: an expert opinion of the Association of Intensive Cardiac Care of the Polish Cardiac Society. Kardiol Pol. 2020; 78(7-8): 825–834.
- Papp Z, Agostoni P, Alvarez J, et al. Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use. Card Fail Rev. 2020; 6: e19.
- Pollesello P, Ben Gal T, Bettex D, et al. Short-Term Therapies for Treatment of Acute and Advanced Heart Failure-Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline? J Clin Med. 2019; 8(11).
- Pölzl G, Altenberger J, Baholli L, et al. Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy. Int J Cardiol. 2017; 243: 389–395.
- Siedlaczek M, Pstrągowski K, Ratajczak J, et al. Cost-effectiveness of levosimendan in patients with exacerbation of chronic heart failure — a single-center perspective. Med Res J. 2021; 6(2): 114–118.
- Kubica A, Kosobucka A, Fabiszak T, et al. Assessment of adherence to medication in patients after myocardial infarction treated with percutaneous coronary intervention. Is there a place for newself-reported questionnaires? Curr Med Res Opin. 2019; 35(2): 341–349.
- Kosobucka A, Michalski P, Pietrzykowski Ł, et al. Adherence to treatment assessed with the Adherence in Chronic Diseases Scale in patients after myocardial infarction. Patient Prefer Adherence. 2018; 12(4): 333–340.
- Kubica A, Obońska K, Fabiszak T, et al. Adherence to antiplatelet treatment with P2Y12 receptor inhibitors. Is there anything we can do to improve it? A systematic review of randomized trials. Curr Med Res Opin. 2016; 32(8): 1441–1451.
- Pietrzykowski Ł, Kasprzak M, Michalski P, et al. Therapy Discontinuation after Myocardial Infarction. J Clin Med. 2020; 9(12).
- Kubica A, Gruchała M, Jaguszewski M, et al. Adherence to treatment — a pivotal issue in long-term treatment of patients with cardiovascular diseases. An expert standpoint. Medical Research Journal. 2018; 2(4): 123–127.
- Pietrzykowski Ł, Michalski P, Kosobucka A, et al. Medication adherence and its determinants in patients after myocardial infarction. Sci Rep. 2020; 10(1): 12028.
- Kubica A. Self-reported questionnaires for a comprehensive assessment of patients after acute coronary syndrome. Med Res J. 2019; 4(2): 106–109.
- Kubica A, Kasprzak M, Obońska K, et al. Discrepancies in assessment of adherence to antiplatelet treatment after myocardial infarction. Pharmacology. 2015; 95(1-2): 50–58.
- Kubica A, Kosobucka A, Michalski P, et al. The adherence in chronic diseases scale-a new tool to monitor implementation of a treatment plan. Folia Cardiol. 2017; 12(1): 19–26.
- Buszko K, Obońska K, Michalski P, et al. The Adherence Scale in Chronic Diseases (ASCD). The power of knowledge: the key to successful patient — health care provider cooperation. Med Res J. 2016; 1(1): 37–42.
- Buszko K, Pietrzykowski Ł, Michalski P, et al. Validation of the Functioning in Chronic Illness Scale (FCIS). Med Res J. 2018; 3(2): 63–69.
- Kubica A, Michalski P, Kasprzak M, et al. Functioning of patients with post-COVID syndrome — preliminary data. Med Res J. 2021; 6(3): 224–229.
- Kubica A, Michalski P, Kasprzak M, et al. Two different approaches to assess adherence to medication in Polish cohort of the EUROASPIRE V registry. Med Res J. 2022; 7(2): 108–113.
- Kubica A. Adherence to medication in elderly patients. Med Res J. 2023; 1(8): 93–94.
- Kubica A, Kubica J. Functioning in chronic disease — a key factor determining adherence to heart failure treatment. Med Res J. 2022; 7(4): 277–279.
- Follath F, Cleland JGF, Just H, et al. Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002; 360(9328): 196–202.
- Fedele F, D'Ambrosi A, Bruno N, et al. Cost-effectiveness of levosimendan in patients with acute heart failure. J Cardiovasc Pharmacol. 2011; 58(4): 363–366.
- de Lissovoy G, Fraeman K, Salon J, et al. The costs of treating acute heart failure: an economic analysis of the SURVIVE trial. J Med Econ. 2008; 11(3): 415–429.
- de Lissovoy G, Fraeman K, Teerlink JR, et al. Hospital costs for treatment of acute heart failure: economic analysis of the REVIVE II study. Eur J Health Econ. 2010; 11(2): 185–193.
- Nieminen MS, Buerke M, Parissis J, et al. Pharmaco-economics of levosimendan in cardiology: a European perspective. Int J Cardiol. 2015; 199: 337–341.