The LEVOECMO trial, led by Alain Combes and colleagues from INSERM and Sorbonne Université, provides one of the most robust evaluations to date of the drug’s role in ECMO-supported shock management.
The study was designed to answer a key clinical question: Can levosimendan help critically ill patients come off VA-ECMO sooner? Despite earlier smaller studies hinting at a possible benefit, the new data show no meaningful advantage.
Conducted across 11 intensive care units in France, the double-blind, placebo-controlled trial enrolled 205 adults between August 2021 and September 2024. All participants had acute cardiogenic shock and had initiated VA-ECMO within the previous 48 hours. They were randomized to receive either levosimendan infusion or placebo, with dosing escalated after two hours.
The following were the key findings of the LEVOECMO trial:
- The primary endpoint of successful ECMO weaning within 30 days was achieved in 68.3% of patients in both the levosimendan and placebo groups.
- In absolute numbers, 69 of 101 patients in the levosimendan group and 71 of 104 in the placebo group were successfully weaned by day 30.
- The hazard ratio for ECMO weaning between the two groups was 1.02, indicating no significant difference.
- Secondary outcomes—including duration of ECMO support, mechanical ventilation, ICU stay, hospital stay, and 60-day mortality—were similar between the groups.
- 60-day mortality was 27.7% in the levosimendan group versus 25% in the placebo group.
- Ventricular arrhythmias occurred more frequently in the levosimendan group (17.8% vs 8.7%), suggesting a potential proarrhythmic risk, though this did not affect overall outcomes.
The authors highlight several limitations. The trial’s original power calculations assumed a much higher weaning failure rate than what occurred, resulting in fewer events than expected. This means smaller treatment effects—if they exist—could have gone undetected. The possibility that specific patient subgroups, such as those with myocarditis, may still benefit cannot be excluded. Additionally, altered pharmacokinetics during ECMO support may reduce drug effectiveness, a phenomenon previously observed in neonates and potentially applicable to adults.
Despite these caveats, the consistent lack of benefit across all endpoints strongly suggests that levosimendan offers no clinical advantage for routine use in ECMO-supported cardiogenic shock.
In summary, the LEVOECMO trial concludes that early levosimendan administration does not shorten ECMO duration, improve recovery, or enhance survival, and therefore cannot be recommended as a standard strategy to facilitate ECMO weaning in this population.
Reference:
Combes A, Saura O, Nesseler N, et al. Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial. JAMA. Published online December 01, 2025. doi:10.1001/jama.2025.19843
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