title: 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: BACKGROUND
  Patients 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
  LICORN 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  NCT02184819 (ClinicalTrials.gov).
authors: Department of Pharmacy, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Thibaut
authors: T
authors: Caruba
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Delphine
authors: D
authors: Hourton
authors: Department of Pharmacy, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.|INSERM Centre de Recherche des Cordeliers UMR S 872 eq 22 Université Paris Descartes, Paris, France.
authors: Brigitte
authors: B
authors: Sabatier
authors: Department of Pharmacy, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Dominique
authors: D
authors: Rousseau
authors: Agence Générale des Equipements et des Produits de Santé (AGEPS), AP-HP, Paris, France.
authors: Annick
authors: A
authors: Tibi
authors: Département de la Recherche Clinique et du Développement (DRCD), Hôpital Saint-Louis, (AP-HP), Paris, France.
authors: Cécile
authors: C
authors: Hoffart-Jourdain
authors: Département de la Recherche Clinique et du Développement (DRCD), Hôpital Saint-Louis, (AP-HP), Paris, France.
authors: Akim
authors: A
authors: Souag
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Nelly
authors: N
authors: Freitas
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Mounia
authors: M
authors: Yjjou
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Carla
authors: C
authors: Almeida
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Nathalie
authors: N
authors: Gomes
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Pascaline
authors: P
authors: Aucouturier
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors: Juliette
authors: J
authors: Djadi-Prat
authors: Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Philippe
authors: P
authors: Menasché
authors: Clinical Trial Unit and INSERM CIC-141, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Gilles
authors: G
authors: Chatellier
authors: Department of Anaesthesiology and Intensive Care, Hôpital Européen Georges Pompidou, AP-HP, 20 rue Leblanc, 75015, Paris, France. bernard.cholley@aphp.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. bernard.cholley@aphp.fr.
authors: Bernard
authors: B
authors: Cholley
mesh_terms: D002303:Cardiac Output, Low / Q000209:etiology / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D001026:Coronary Artery Bypass / Q000379:methods / Q000401:mortality; D004311:Double-Blind Method; D006353:Heart-Assist Devices; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D059035:Perioperative Period; D011724:Pyridazines / Q000627:therapeutic use*; D017582:Renal Replacement Therapy; D012107:Research Design; D000077464:Simendan; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000150:complications*
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan
keywords: Cardiac surgery; Coronary artery bypass graft; High risk surgical patient; Levosimendan; Low cardiac output syndrome; Perioperative management