Short- and Long-term Efficacy and Safety of Levosimendan in Veno-arterial Extracorporeal Membrane Oxygenation Weaning: The WEANILEVO Randomized Double-Blind Multicenter Trial.

Abstract

Liberation from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) remains challenging. To date, there is limited evidence from observational studies supporting pharmacologic interventions to facilitate successful VA-ECMO weaning. The current 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. 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 -1 · min -1 ) or placebo for 24 h. The primary endpoint was VA-ECMO weaning failure, defined as absence of weaning within 48 h, recourse to another circulatory assistance device, or death within 7 days of weaning. 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 (odds ratio, 1.00 [95% confidence interval, 0.36 to 2.75]; P = 1.00). Acute kidney injury at day 30 was significantly more frequent in the levosimendan group (62.5% vs . 38.5%; odds ratio, 2.67 [95% confidence interval, 1.08 to 6.62]; P = 0.03). Patients receiving levosimendan required more vasopressor support (47.5% vs . 28.2%; P = 0.07) and had longer intensive care unit stays (12 [7 to 24] vs . 6 [4 to 13] days; P = 0.02). Mortality rates at 30 days (18.0% vs . 33.3%; P = 0.07) and 1 yr (31.6% vs . 51.4%; P = 0.08) did not significantly differ between groups. 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 intensive care unit stays in the levosimendan group are hypothesis generating and require confirmation in larger, adequately powered trials.