Short- and Long-Term Efficacy and Safety of Levosimendan in VA-ECMO Weaning: The WEANILEVO Randomized Double-Blind Multicenter Trial

BACKGROUND: Liberation from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) remains challenging. To date, we have limited evidence from observational studies supporting pharmacological interventions to facilitate successful VA-ECMO weaning. The present study aimed to evaluate the efficacy and safety of a single dose of levosimendan in patients supported by VA-ECMO who met predefined criteria for weaning. METHODS: The WEANILEVO study was a multicenter, double-blind, randomized, parallel-group, placebo-controlled trial. Eighty patients from five French centers who met VA-ECMO weaning criteria were randomly assigned 1:1 to receive either levosimendan (0.2 μg/kg/min) or placebo for 24 hours. The primary endpoint was VA-ECMO weaning failure, defined as absence of weaning within 48 hours, recourse to another circulatory assistance device, or death within 7 days of weaning. RESULTS: Due to halted funding, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 80 patients (40 in the levosimendan group and 40 in the control group). VA-ECMO weaning failure occurred in 25% of patients in both the levosimendan and placebo groups (OR=1.00 [95%CI: 0.36-2.75], p=1.00). Acute kidney injury at day 30 was significantly more frequent in the levosimendan group (62.5% vs. 38.5%; OR=2.67 [95%CI: 1.08-6.62], p=0.03). Patients receiving levosimendan required more vasopressor support (47.5% vs. 28.2%, p=0.07) and had longer ICU stays (12 [7-24] vs. 6 [4-13] days, p=0.02). Mortality rates at 30 days (18.0% vs. 33.3%, p=0.07) and 1 year (31.6% vs. 51.4%, p=0.08) did not significantly differ between groups. CONCLUSIONS: Levosimendan administration did not reduce VA-ECMO weaning failure in patients who already met weaning criteria; however, a clinically important benefit or harm cannot be ruled out. The observed higher incidence of acute kidney injury and longer ICU stays in the levosimendan group are hypothesis-generating and require confirmation in larger, adequately powered trials.REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT04158674.