Mehta Rajendra H, Van Diepen Sean, Meza James, Bokesch Paula, Leimberger Jeffrey D, Tourt-Uhlig Sandra, Swartz Merri, Parrotta Jodi, Jankowich Rachael, Hay Douglas, Harrison Robert W, Fremes Stephen, Goodman Shaun G, Luber John, Toller Wolfgang, Heringlake Matthias, Anstrom Kevin J, Levy Jerrold H, Harrington Robert A, Alexander John H
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
Canadian VIGOUR Centre, University of Alberta, Alberta, Edmonton, Canada.
Am Heart J. 2016 Dec;182:62-71. doi: 10.1016/j.ahj.2016.09.001. Epub 2016 Sep 9.
Low cardiac output syndrome is associated with increased mortality and occurs in 3% to 14% of patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Levosimendan, a novel calcium sensitizer and K channel activator with inotropic, vasodilatory, and cardioprotective properties, has shown significant promise in reducing the incidence of low cardiac output syndrome and related adverse outcomes in patients undergoing cardiac surgery on CPB.
LEVO-CTS is a phase 3 randomized, controlled, multicenter study evaluating the efficacy, safety, and cost-effectiveness of levosimendan in reducing morbidity and mortality in high-risk patients with reduced left ventricular ejection fraction (≤35%) undergoing cardiac surgery on CPB. Patients will be randomly assigned to receive either intravenous levosimendan (0.2 μg kg min for the first hour followed by 0.1 μg/kg for 23hours) or matching placebo initiated within 8hours of surgery. The co-primary end points are (1) the composite of death or renal replacement therapy through day 30 or perioperative myocardial infarction, or mechanical assist device use through day 5 (quad end point tested at α<.01), and (2) the composite of death through postoperative day 30 or mechanical assist device use through day 5 (dual end point tested at α<.04). Safety end points include new atrial fibrillation and death through 90days. In addition, an economic analysis will address the cost-effectiveness of levosimendan compared with placebo in high-risk patients undergoing cardiac surgery on CPB. Approximately 880 patients will be enrolled at approximately 60 sites in the United States and Canada between July 2014 and September 2016, with results anticipated in January 2017.
LEVO-CTS, a large randomized multicenter clinical trial, will evaluate the efficacy, safety, and cost-effectiveness of levosimendan in reducing adverse outcomes in high-risk patients undergoing cardiac surgery on CPB.
ClinicalTrials.gov (NCT02025621).
低心排血量综合征与死亡率增加相关，在接受体外循环（CPB）心脏手术的患者中发生率为3%至14%。左西孟旦是一种新型钙增敏剂和钾通道激活剂，具有正性肌力、血管舒张和心脏保护特性，在降低接受CPB心脏手术患者的低心排血量综合征发生率及相关不良结局方面已显示出显著前景。
LEVO-CTS是一项3期随机、对照、多中心研究，旨在评估左西孟旦在降低接受CPB心脏手术的左心室射血分数降低（≤35%）高危患者的发病率和死亡率方面的疗效、安全性和成本效益。患者将被随机分配接受静脉注射左西孟旦（第1小时0.2μg/kg·min，随后23小时0.1μg/kg）或在手术8小时内开始使用的匹配安慰剂。共同主要终点为：（1）至第30天死亡或肾脏替代治疗、或围手术期心肌梗死、或至第5天使用机械辅助装置的复合终点（四重终点，α<0.01检验）；（2）至术后第30天死亡或至第5天使用机械辅助装置的复合终点（双重终点，α<0.04检验）。安全终点包括90天内新发房颤和死亡。此外，一项经济学分析将探讨左西孟旦与安慰剂相比在接受CPB心脏手术的高危患者中的成本效益。2014年7月至2016年9月期间，美国和加拿大约60个地点将招募约880例患者，预计2017年1月得出结果。
LEVO-CTS是一项大型随机多中心临床试验，将评估左西孟旦在降低接受CPB心脏手术的高危患者不良结局方面的疗效、安全性和成本效益。
ClinicalTrials.gov（NCT02025621）
