| Title: |
Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock |
| Authors: |
Combes, Alain; Saura, Ouriel; Nesseler, Nicolas; Lebbah, Said; Rozec, Bertrand; Levy, Bruno; Fellahi, Jean-Luc; Beurton, Antoine; Meslin, Simon; Gaudard, Philippe; Bouglé, Adrien; Vincentelli, André; Sonneville, Romain; Lebreton, Guillaume; Lévy, David; Ouattara, Alexandre; Tubach, Florence; Chommeloux, Juliette; del Marmol, Grégoire; Hekimian, Guillaume; Leprince, Pascal; Luyt, Charles-Edouard; Moyon, Quentin; Pineton, Marc; Schmidt, Matthieu; Djavidi, Nima; Batsale, Corinne; Besnard, Thibaud; Hérion, François-Xavier; Imbault, Julien; Maudiere, Laure; Oddos, Claire; Pernot, Mathieu; Veyret, Simon; Dachraoui, Najla; Gimbert, Florence; Nougue, Hélène; Achouh, Paul; Cholley, Bernard; Chesnel, Delphine; Didier, Léa; Jacquet-Lagreze, Matthias; Ruste, Martin; Pierre, Joseph; Ughetto, Aurore; David, Hélène; Mourad, Marc; Blin, Cinderella; Biedermann, Sebastien; Buzin, Xavier; Flécher, Erwan; Le Gac, Grégoire; Mansour, Alexandre; Kimmoun, Antoine; Perez, Pierre; Haddadi, Clement; Thivillier, Carine; Klein, Thomas; Bailly, Arthur; Bizouarn, Philippe; Cadiet, Julien; Groleau, Nicolas; Lepoivre, Thierry; Nicolet, Johanna; Souab, Fouzia; Vourc'H, Mickaël; Jungling, Marie; de Montmollin, Etienne; Bouadma, Lila; Timsit, Jean-François; Thy, Michael; Dessajan, Julien |
| Contributors: |
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition CHU Pitié Salpêtrière (IHU ICAN); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Centre d'Investigation Clinique Rennes (CIC); Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM); Nutrition, Métabolismes et Cancer (NuMeCan); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Institut du Thorax CHU Nantes (CHU Thorax); Centre Inria de l'Université Paris-Saclay; Centre Inria de Saclay; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria); Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases (BMC); Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM); Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO); Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Groupe de Recherche Clinique en Anesthésie Réanimation médecine PEriopératoire (GRC 29 - ARPE); Sorbonne Université (SU); Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord; Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Pharmacoépidémiologie et évaluation des soins iPLesp (PEPITES); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); The trial was financed by a grant from the French Ministry of Health (PHRC APHP-P170914J) and was sponsored by the Direction de la Recherche Clinique et du Développement, Assistance Publique–Hôpitaux de Paris. Orion Pharmaceuticals provided levosimendan and placebo free of charge. |
| Source: |
ISSN: 2380-6583. |
| Publisher Information: |
CCSD; American Medical Association |
| Publication Year: |
2026 |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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, ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41324946; PUBMED: 41324946; WOS: 001631162500001 |
| DOI: |
10.1001/jama.2025.19843 |
| Availability: |
https://hal.science/hal-05392447; https://doi.org/10.1001/jama.2025.19843 |
| Accession Number: |
edsbas.E6109B29 |
| Database: |
BASE |