Robinson Sian, Zincuk Aleksander, Larsen Ulla Lei, Ekstrøm Claus, Toft Palle
Department of Anesthesia and Intensive Care, Odense University Hospital, Sdr, Boulevard 29, Odense C DK 5000, Denmark.
Trials. 2014 Jun 13;15:226. doi: 10.1186/1745-6215-15-226.
Previous pharmacokinetic trials suggested that 40 mg subcutaneous enoxaparin once daily provided inadequate thromboprophylaxis for intensive care unit patients. Critically ill patients with acute kidney injury are at increased risk of venous thromboembolism and yet are often excluded from these trials. We hypothesized that for critically ill patients with acute kidney injury receiving continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously once daily would improve thromboprophylaxis without increasing the risk of bleeding. In addition, we seek to utilize urine output prior to discontinuing dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free intervals, as markers of renal recovery.
METHODS/DESIGN: In a multicenter, double-blind randomized controlled trial in progress at three intensive care units across Denmark, we randomly assign eligible critically ill adults with acute kidney injury into a treatment (1 mg/kg enoxaparin subcutaneously once daily) or control arm (40 mg enoxaparin subcutaneously once daily) upon commencement of continuous renal replacement therapy.We calculated that with 133 patients in each group, the study would have 80% power to show a 40% reduction in the relative risk of venous thromboembolism with 1 mg/kg enoxaparin, at a two-sided alpha level of 0.05. An interim analysis will be conducted after the first 67 patients have been included in each group.Enrolment began in March 2013, and will continue for two years. The primary outcome is the occurrence of venous thromboembolism. Secondary outcomes include anti-factor Xa activity, bleeding, heparin-induced thrombocytopenia, filter lifespan, length of stay, ventilator free days, and mortality. We will also monitor neutrophil gelatinase-associated lipocalin and urine volume to determine whether they can be used as prognostic factors for renal recovery.
Critically ill unit patients with acute kidney injury present a particular challenge in the provision of thromboprophylaxis. This study hopes to add to the growing evidence that the existing recommendation of 40 mg enoxaparin is inadequate and that 1 mg/kg is both safe and effective for thromboprophylaxis.In addition, the study seeks to identify predictors of renal recovery allowing for the proper utilization of resources.
EU Clinical Trials Register: EudraCT number: 2012-004368-23, 25 September 2012.
既往的药代动力学试验表明，对于重症监护病房患者，每日皮下注射40毫克依诺肝素的血栓预防效果不佳。患有急性肾损伤的重症患者发生静脉血栓栓塞的风险增加，但这些试验往往将他们排除在外。我们推测，对于接受持续肾脏替代治疗的急性肾损伤重症患者，每日皮下注射1毫克/千克依诺肝素的剂量可改善血栓预防效果，且不会增加出血风险。此外，我们试图利用停止透析前的尿量以及无透析间期低水平的中性粒细胞明胶酶相关脂质运载蛋白作为肾脏恢复的标志物。
方法/设计：在丹麦三个重症监护病房正在进行的一项多中心、双盲随机对照试验中，我们在 eligible critically ill adults with acute kidney injury into a treatment (1 mg/kg enoxaparin subcutaneously once daily) or control arm (40 mg enoxaparin subcutaneously once daily) upon commencement of continuous renal replacement therapy.每组纳入133例患者的情况下，本研究将有80%的把握度在双侧α水平为0.05时，显示1毫克/千克依诺肝素使静脉血栓栓塞相对风险降低40%。每组纳入67例患者后将进行中期分析。入组于2013年3月开始，将持续两年。主要结局是静脉血栓栓塞的发生。次要结局包括抗Xa因子活性、出血、肝素诱导的血小板减少症、滤器使用寿命、住院时间、无呼吸机天数和死亡率。我们还将监测中性粒细胞明胶酶相关脂质运载蛋白和尿量，以确定它们是否可作为肾脏恢复的预后因素。
对于患有急性肾损伤的重症监护病房患者，在提供血栓预防方面存在特殊挑战。本研究希望补充越来越多的证据，即现有的40毫克依诺肝素推荐剂量不足，而1毫克/千克剂量在血栓预防方面既安全又有效。此外，该研究旨在确定肾脏恢复的预测因素，以便合理利用资源。
欧盟临床试验注册：EudraCT编号：2012 - 004368 - 23，2012年9月25日。 （注：原文中“eligible critically ill adults with acute kidney injury into a treatment...”部分表述似乎不完整，但按照要求未添加解释或说明直接翻译）
