NCT04728932: LEVOECMO

LEVOSIMENDAN to Facilitate Weaning From ECMO in Severe Cardiogenic Shock Patients

Completed Phase 3 Last updated 21 March 2025

What this trial tests

Phase 3 trial testing Levosimendan in Cardiogenic Shock in 206 participants. Completed in 9 November 2024.

Timeline

27 August 2021

Primary endpoint
9 November 2024

9 November 2024

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	206
Start date	27 August 2021
Primary completion	9 November 2024
Estimated completion	9 November 2024
Sites	3 locations across France

Drugs / interventions tested

• Levosimendan (LEVOSIMENDAN) — full drug profile →
• Placebo of Levosimendan — full drug profile →

Conditions studied

• Cardiogenic Shock — all drugs for Cardiogenic Shock →
• Extracorporeal Membrane Oxygenation Complication — all drugs for Extracorporeal Membrane Oxygenation Complication →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Cardiogenic Shock or Extracorporeal Membrane Oxygenation Complication. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

In the last decade, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become the first-line therapy in patients with refractory cardiogenic shock. VA-ECMO provides both respiratory and cardiac support, is easy to insert, even at the bedside, provides stable flow rates, and is associated with less organ failure after implantation compared to large biventricular assist-devices that require open-heart surgery. In patients with potentially reversible cardiac failure (e.g. myocarditis, myocardial stunning post-myocardial infarction, post-cardiotomy or post-cardiac arrest), VA-ECMO might be weaned after a few days of support and used as a bridge to recovery.

Although considered as the ultimate life-saving technology for refractory cardiac failure, veno-arterial ECMO is still associated with severe complications. Specifically, excessive LV afterload and lack of LV unloading under VA-ECMO might induce LV stasis with thrombus formation, pulmonary edema, myocardial ischemia caused by ventricular distension and ultimately increase mortality. ECMO support also exposes to many complications such as infections, hemorrhage or peripheral vascular embolism. These complications are more frequent with prolonged support and are responsible for significant morbidity and mortality, prolonged ICU and hospital stays and higher costs.

Levosimendan, which acts to sensitize myocardial contractile proteins to calcium, improves cardiac contractility without increasing the intracellular calcium concentration. Unlike traditional inotropes such as dobutamine, levosimendan neither increases myocardial oxygen consumption nor impairs diastolic function or possess proarrhythmic effects. It also influences the opening of ATP-dependent potassium channels, including those in vascular smooth muscle cells, leading to coronary, pulmonary, and peripheral vasodilation and antiinflammatory, antioxidative, antiapoptotic, anti-stunning and cardioprotective effects. Additionally, Levosimendan which has a long lasting action (up to 7-9 d), resulting from the formation of active metabolite, may be used as a single 24h perfusion.

In recent preliminary studies, the drug was associated with accelerated weaning from VA-ECMO and even improved survival. Therefore, a multicenter randomized trial with sufficient statistical power is needed in refractory cardiogenic shock patients supported by VA-ECMO to test if the early administration of Levosimendan can facilitate and accelerate VA-ECMO weaning, and ultimately translate in significantly less morbidity, reduced ICU and hospital length of stays and associated costs.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap.
   Conti N, Gatti M, Raschi E, Diemberger I, et al · · 2021 · cited 19× · PMID 34376973 · DOI 10.2147/dddt.s295214
2. Levosimendan in patients undergoing extracorporeal membrane oxygenation after cardiac surgery: an emulated target trial using observational data.
   Massol J, Simon-Tillaux N, Tohme J, Hariri G, et al · · 2023 · cited 10× · PMID 36750852 · DOI 10.1186/s13054-023-04328-6
3. Levosimendan to Facilitate Weaning From Cardiorespiratory Support in Critically Ill Patients: A Meta-Analysis.
   Luo JC, Zheng WH, Meng C, Zhou H, et al · · 2021 · cited 10× · PMID 34712681 · DOI 10.3389/fmed.2021.741108
4. Early Levosimendan Administration Improved Weaning Success Rate in Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock.
   Chen YW, Lee WC, Wu PJ, Fang HY, et al · · 2022 · cited 7× · PMID 35845047 · DOI 10.3389/fcvm.2022.912321
5. Levosimendan for VA-ECMO weaning: the silver lining.
   Kaddoura R, Mohamed Ibrahim MI, Omar A. · · 2022 · cited 7× · PMID 34873878 · DOI 10.1002/ehf2.13751
6. Does Levosimendan hasten veno-arterial ECMO weaning? A propensity score matching analysis.
   Paulo N, Kimmoun A, Hajage D, Hubert P, et al · · 2025 · cited 4× · PMID 40180673 · DOI 10.1186/s13613-025-01457-9
7. Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial.
   Combes A, Saura O, Nesseler N, Lebbah S, et al · · 2026 · cited 3× · PMID 41324946 · DOI 10.1001/jama.2025.19843
8. Clinical outcomes of levosimendan administration in veno-arterial extracorporeal membrane oxygenation: a meta-analysis.
   Zhao GM, Zhao GM, Zhang H, Chen W, et al · · 2025 · cited 1× · PMID 41033771 · DOI 10.1136/bmjopen-2025-101995