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Clinical Trial
. 2026 Jan 6;335(1):60-69.
doi: 10.1001/jama.2025.19843.

Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial

Alain Combes  1   2 , Ouriel Saura  1   2 , Nicolas Nesseler  3 , Said Lebbah  4 , Bertrand Rozec  5   6 , Bruno Levy  7   8   9 , Jean-Luc Fellahi  10   11 , Antoine Beurton  12   13 , Simon Meslin  14 , Philippe Gaudard  15 , Adrien Bouglé  16   17 , André Vincentelli  18 , Romain Sonneville  19   20 , Guillaume Lebreton  1   21 , David Lévy  1   2 , Alexandre Ouattara  12   13 , Florence Tubach  4   22 ; LEVOECMO Trial Group and the International ECMO Network (ECMONet)
Collaborators, Affiliations
Clinical Trial

Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial

Alain Combes et al. JAMA. .

Abstract

Importance: Levosimendan may facilitate weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) and improve survival, but supporting evidence remains limited.

Objective: To assess whether early administration of levosimendan reduces the time to successful VA-ECMO weaning in patients with severe but potentially reversible cardiogenic shock.

Design, setting, and participants: Randomized, double-blind, placebo-controlled trial conducted across 11 intensive care units (ICUs) in France. Between August 27, 2021, and September 10, 2024, 205 adult patients with acute cardiogenic shock who had started VA-ECMO in the preceding 48 hours were enrolled. Final follow-up was completed on November 10, 2024.

Interventions: Patients were randomized in a 1:1 ratio to receive levosimendan, 0.15 μg/kg per minute, to be increased to 0.20 μg/kg per minute after 2 hours (n = 101), or placebo (n = 104).

Main outcomes and measures: The primary outcome was time to successful ECMO weaning within 30 days following randomization. Secondary outcomes included ECMO-, mechanical ventilation-, and organ failure-free days, ICU and hospital lengths of stay, serious adverse events, and all-cause 30- and 60-day mortality.

Results: Among the 205 randomized patients (median age, 58 [IQR, 50-67] years; 149 [72.7%] male), main cardiogenic shock etiologies were postcardiotomy (79 [38.5%]), acute myocardial infarction (56 [27.3%]), and myocarditis (28 [13.7%]). Treatment dose was increased to 0.20 ± 0.01 μg/kg per minute in 93% of patients receiving levosimendan and in 96% of those receiving placebo. Within 30 days, 69 of 101 patients (68.3%) had a successful ECMO weaning in the levosimendan group compared with 71 of 104 (68.3%) in the placebo group (risk difference, 0.0% [95% CI, -12.8% to 12.7%]; subdistribution hazard ratio, 1.02 [95% CI, 0.74-1.39]; P = .92). In the levosimendan and placebo groups, respectively, median ECMO duration (5 [IQR, 4-7] days vs 6 [IQR, 4-11] days; P = .53), mean ICU length of stay (18 [SD, 15] days vs 19 [SD, 15] days; P = .42), and 60-day mortality (27.7% vs 25.0%; risk difference, 2.7% [95% CI, -9.0% to 15.3%]; P = .78) did not differ significantly. Ventricular arrhythmias occurred more frequently with levosimendan (18 [17.8%] vs 9 [8.7%]; absolute risk difference, 9.2% [95% CI, 0.4%-18.1%]).

Conclusions and relevance: Among patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo.

Trial registration: ClinicalTrials.gov Identifier: NCT04728932.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Combes reported receipt of personal fees from Getinge and Baxter and grants from Getinge. Dr B. Levy reported receipt of personal fees from Orion. Dr Ouattara reported receipt of personal fees from Orion as member of an advisory board and for giving invited lectures at industry symposia. No other disclosures were reported.

Comment on

References

    1. Combes A, Price S, Slutsky AS, Brodie D. Temporary circulatory support for cardiogenic shock. Lancet. 2020;396(10245):199-212. doi: 10.1016/S0140-6736(20)31047-3 - DOI - PubMed
    1. Cholley B, Bojan M, Guillon B, et al. ; ARCOTHOVA Study Group . Overview of the current use of levosimendan in France: a prospective observational cohort study. Ann Intensive Care. 2023;13(1):69. doi: 10.1186/s13613-023-01164-3 - DOI - PMC - PubMed
    1. Jamali IN, Kersten JR, Pagel PS, Hettrick DA, Warltier DC. Intracoronary levosimendan enhances contractile function of stunned myocardium. Anesth Analg. 1997;85(1):23-29. - PubMed
    1. Papp Z, Édes I, Fruhwald S, et al. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012;159(2):82-87. doi: 10.1016/j.ijcard.2011.07.022 - DOI - PubMed
    1. Mebazaa A, Nieminen MS, Packer M, et al. ; SURVIVE Investigators . Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA. 2007;297(17):1883-1891. doi: 10.1001/jama.297.17.1883 - DOI - PubMed

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