Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (≤40 %) undergoing CABG with cardiopulmonary bypass (LICORN study)

Abstract

BackgroundPatients with a left ventricular ejection fraction (LVEF) of less than 40 % are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite actual treatments (inotropic agents and/or mechanical assist devices), the mortality rate of such patients remains very high (13 to 24 %). The LICORN trial aims at assessing the efficacy of a preoperative infusion of levosimendan in reducing postoperative LCOS in patients with poor LVEF undergoing coronary artery bypass grafting (CABG).Methods/DesignLICORN study is a multicenter, randomized double-blind, placebo-controlled trial in parallel groups. 340 patients with LVEF ≤40 %, undergoing CABG will be recruited from 13 French hospitals. The study drug will be started after anaesthesia induction and infused over 24 h (0.1 μg/kg/min).The primary outcome (postoperative LCOS) is evaluated using a composite criterion composed of: 1) need for inotropic agents beyond 24 h following discontinuation of the study drug; 2) need for post-operative mechanical assist devices or failure to wean from these techniques when inserted pre-operatively; 3) need for renal replacement therapy. Secondary outcomes include: 1) mortality at Day 28 and Day 180; 2) each item of the composite criterion of the primary outcome; 3) the number of “ventilator-free” days and “out of intensive care unit” days at Day 28.DiscussionThe usefulness of levosimendan in the perioperative period has not yet been documented with a high level of evidence. The LICORN study is the first randomized controlled trial evaluating the clinical value of preoperative levosimendan in high risk cardiac surgical patients undergoing CABG.Trial registration numberNCT02184819 (ClinicalTrials.gov).

Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta-analysis

“…The dose of levosimendan differed among most trials. It is proposed that higher bolus doses of levosimendan may be more effective . However, such regimens have been showed to be associated with a higher incidence of adverse events and less survival in other studies .…”

Levosimendan in patients with low ejection fraction undergoing cardiac surgery

“…Another multicenter study, dubbed with the acronym LICORN, was conducted in 13 hospitals in France to assess the efficacy of levosimendan in preventing low cardiac output syndrome after CABG [ 9 ]. Levosimendan was administered after anesthesia, dosed at 0.1 μg/kg/min, to patients with left ventricular ejection fraction ≤ 35%.…”

“…Data from small randomized studies and meta-analyses indicate that levosimendan is effective in preventing and treating low cardiac output syndrome. The results of large randomized studies published in 2016 and 2017 offer less optimism [ 1 , 8 , 9 ]. The current debate on the effectiveness of levosimendan focuses on the time of its administration, which may prove to be a key element of the therapy.…”

Effect of levosimendan on prognosis in adult patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials

“…Many patients with advanced stages of cardiac disease need cardiac surgery, which can lead to severe left ventricular dysfunction and, in particular, postoperative low cardiac output syndrome (LCOS) [ 1 ]. These conditions may lead to increased morbidity, multiple organ failure and death [ 2 ]. Strategies to address the syndrome include the use of inotropic agents and an intra-aortic balloon pump (IABP).…”