Uncontrolled bleeding after cardiac surgery can be life-threatening. Factor eight inhibitor bypassing activity (FEIBA) is a prothrombin complex concentrate empirically used as rescue therapy for correction of refractory bleeding diathesis post-cardiopulmonary bypass (CPB). FEIBA used as rescue therapy for bleeding diathesis after CPB has been associated with a low incidence of complications and a reduction in transfusion requirement and re-exploration. The feasibility and efficacy of early administration of FEIBA after the termination of CPB have not been studied in a prospective randomized trial. We designed a small randomized, double-blinded, placebo-controlled pilot trial to determine the feasibility of a larger trial testing the hypothesis that FEIBA decreases transfusion requirements after CPB. The study was designed to evaluate the feasibility of a larger pivotal trial to determine the effectiveness of FEIBA in reducing the total volume of blood products transfused perioperatively, and its safety profile. Study participants were adult patients undergoing elective major aortic cardiovascular surgery at a tertiary referral hospital, who were equally randomized to receive a single dose of either FEIBA or matched placebo intraoperatively at the end of CPB. Twenty patients were screened and 12 were randomized and included in the analysis. Protocol adherence was high, and all patients received the study drug per intention-to-treat except one patient. There were no protocol deviations or events of unblinding, and adverse events were not different between groups. Patients in the FEIBA group were older and more likely to be female and had higher BMI, lower hematocrit, and longer hypothermic circulatory arrest. There were no differences in post-randomization blood product transfusions (difference FEIBA vs. placebo −899 mL; 95% CI −5206 to 3409) or in the administration of open-label FEIBA. This pilot trial confirmed the adequacy of the trial design that involved the early, blinded administration of FEIBA, by demonstrating excellent protocol adherence. We conclude that a larger trial establishing the effectiveness of early prothrombin complex concentrate administration to reduce the use of blood products in the setting of high-risk cardiac surgery is feasible. ClinicalTrials.gov, NCT02577614 . Registered 16 October 2015

中文翻译：

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用于减少心脏手术输血的因子 VIII 抑制剂旁路活性 (FEIBA)：一项随机、双盲、安慰剂对照、先导试验

心脏手术后不受控制的出血可能会危及生命。因子八抑制剂旁路活性 (FEIBA) 是一种凝血酶原复合物浓缩物，经验性地用作纠正体外循环 (CPB) 后难治性出血素质的救援疗法。FEIBA 用作 CPB 后出血素质的抢救治疗与并发症发生率低以及输血需求和重新探查的减少有关。尚未在前瞻性随机试验中研究 CPB 终止后早期给予 FEIBA 的可行性和有效性。我们设计了一项小型随机、双盲、安慰剂对照试验，以确定大型试验的可行性，以检验 FEIBA 减少 CPB 后输血需求的假设。该研究旨在评估一项更大的关键试验的可行性，以确定 FEIBA 在减少围手术期输血总量方面的有效性及其安全性。研究参与者是在三级转诊医院接受择期主要主动脉心血管手术的成年患者，他们在 CPB 结束时同样随机接受单剂量的 FEIBA 或术中匹配的安慰剂。筛选了 20 名患者，其中 12 名被随机分配并纳入分析。方案依从性高，除一名患者外，所有患者均按意向治疗接受研究药物。没有方案偏差或揭盲事件，并且组间的不良事件没有差异。FEIBA 组的患者年龄更大，更可能是女性，BMI 更高，血细胞比容更低，低温停循环时间更长。随机化后的血液制品输注（FEIBA 与安慰剂的差异 -899 mL；95% CI -5206 至 3409）或开放标签 FEIBA 的给药没有差异。该试点试验通过展示出色的方案依从性，证实了涉及 FEIBA 早期、盲法给药的试验设计的充分性。我们得出结论，一项更大规模的试验确定早期凝血酶原复合浓缩物给药以减少高危心脏手术中血液制品使用的有效性是可行的。ClinicalTrials.gov，NCT02577614。2015 年 10 月 16 日注册 随机化后的血液制品输注（FEIBA 与安慰剂的差异 -899 mL；95% CI -5206 至 3409）或开放标签 FEIBA 的给药没有差异。该试点试验通过展示出色的方案依从性，证实了涉及 FEIBA 早期、盲法给药的试验设计的充分性。我们得出结论，一项更大规模的试验确定早期凝血酶原复合浓缩物给药以减少高危心脏手术中血液制品使用的有效性是可行的。ClinicalTrials.gov，NCT02577614。2015 年 10 月 16 日注册 随机化后的血液制品输注（FEIBA 与安慰剂的差异 -899 mL；95% CI -5206 至 3409）或开放标签 FEIBA 的给药没有差异。该试点试验通过展示出色的方案依从性，证实了涉及 FEIBA 早期、盲法给药的试验设计的充分性。我们得出结论，一项更大规模的试验确定早期凝血酶原复合浓缩物给药以减少高危心脏手术中血液制品使用的有效性是可行的。ClinicalTrials.gov，NCT02577614。2015 年 10 月 16 日注册 该试点试验通过展示出色的方案依从性，证实了涉及 FEIBA 早期、盲法给药的试验设计的充分性。我们得出结论，一项更大规模的试验确定早期凝血酶原复合浓缩物给药以减少高危心脏手术中血液制品使用的有效性是可行的。ClinicalTrials.gov，NCT02577614。2015 年 10 月 16 日注册 该试点试验通过展示出色的方案依从性，证实了涉及 FEIBA 早期、盲法给药的试验设计的充分性。我们得出结论，一项更大规模的试验确定早期凝血酶原复合浓缩物给药以减少高危心脏手术中血液制品使用的有效性是可行的。ClinicalTrials.gov，NCT02577614。2015 年 10 月 16 日注册