Alain Combes, Ouriel Saura, Nicolas Nesseler, Saïd Lebbah, Bertrand Rozec, Bruno Lévy, Jean-Luc Fellahi, Antoine Beurton, Simon Meslin, Philippe Gaudard, Adrien Bouglé, André Vincentelli, Romain Sonneville, Guillaume Lebreton, David Lévy, Alexandre Ouattara, Florence Tubach, LEVOECMO Trial Group and the International ECMO Network (ECMONet), Juliette Chommeloux, Grégoire Del Marmol, Guillaume Hékimian, P. Leprince, Charles‐Édouard Luyt, Quentin Moyon, Marc Pineton, Matthieu Schmidt, Nima Djavidi, Corinne Batsale, Thibaud Besnard, François-Xavier Hérion, Julien Imbault, Laure Maudiere, Claire Oddos, Mathieu Pernot, Simon Veyret, Najla DACHRAOUI, Florence GIMBERT, Hélène Nougue, Paul Achouh, Bernard Cholley, Delphine Chesnel, Léa Didier, Matthias Jacquet‐Lagrèze, Martin Ruste, Jeannier Pierre, Aurore Ughetto, Hélène David, Marc Mourad, Cinderella Blin, Sébastien Biedermann, Xavier Buzin, Erwan Flécher, Grégoire Le Gac, Alexandre Mansour, Antoine Kimmoun, Pierre Perez, Clément Haddadi, Carine Thivillier, Thomas Klein, Arthur Bailly, Philippe Bizouarn, Julien Cadiet, Nicolas Groleau, Thierry Lepoivre, Johanna Nicolet, Fouzia Souab, Mickaël Vourc’h, Marie Jungling, Étienne de Montmollin, Lila Bouadma, Jean-François Timsit, Michaël Thy, Julien Dessajan
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.