Aims Ciraparantag is a reversal agent for anticoagulants including direct oral anticoagulants. The aim was to evaluate the efficacy and safety of ciraparantag to reverse anticoagulation induced by apixaban or rivaroxaban in healthy elderly adults. Methods and results Two randomized, placebo-controlled, dose-ranging trials conducted in healthy subjects aged 50–75 years. Subjects received apixaban (Study 1) 10 mg orally twice daily for 3.5 days or rivaroxaban (Study 2) 20 mg orally once daily for 3 days. At steady-state anticoagulation subjects were randomized 3:1 to a single intravenous dose of ciraparantag (Study 1: 30, 60, or 120 mg; Study 2: 30, 60, 120, or 180 mg) or placebo. Efficacy was based on correction of the whole blood clotting time (WBCT) at multiple timepoints over 24 h. Subjects and technicians performing WBCT testing were blinded to treatment. Complete reversal of WBCT within 1 h post-dose and sustained through 5 h (apixaban) or 6 h (rivaroxaban) was dose related and observed with apixaban in 67%, 100%, 100%, and 17% of subjects receiving ciraparantag 30 mg, 60 mg, 120 mg, or placebo, respectively; and with rivaroxaban in 58%, 75%, 67%, 100%, and 13% of subjects receiving ciraparantag 30 mg, 60 mg, 120 mg, 180 mg, or placebo, respectively. Adverse events related to ciraparantag were mild, transient hot flashes or flushing. Conclusions Ciraparantag provides a dose-related reversal of anticoagulation induced by steady-state dosing of apixaban or rivaroxaban. Sustained reversal was achieved with 60 mg ciraparantag for apixaban and 180 mg ciraparantag for rivaroxaban. All doses of ciraparantag were well tolerated.

中文翻译：

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Ciraparantag 可逆转健康老年受试者中阿哌沙班和利伐沙班的抗凝活性

目的 Ciraparantag 是一种抗凝剂的逆转剂，包括直接口服抗凝剂。目的是评估西拉帕那他逆转阿哌沙班或利伐沙班在健康老年人中诱导的抗凝作用的有效性和安全性。方法和结果 在 50-75 岁的健康受试者中进行的两项随机、安慰剂对照、剂量范围试验。受试者接受阿哌沙班（研究 1）10 mg 每天两次口服，持续 3.5 天或利伐沙班（研究 2）20 mg，每天一次口服，持续 3 天。在稳态抗凝时，受试者以 3:1 的比例随机分配至单次静脉注射 ciraparantag（研究 1：30、60 或 120 mg；研究 2：30、60、120 或 180 mg）或安慰剂。功效基于在 24 小时内多个时间点的全血凝固时间 (WBCT) 校正。进行 WBCT 测试的受试者和技术人员对治疗不知情。给药后 1 小时内 WBCT 完全逆转并持续至 5 小时（阿哌沙班）或 6 小时（利伐沙班）与剂量相关，在接受阿哌沙班 30 mg 的受试者中观察到 67%、100%、100% 和 17% , 60 毫克, 120 毫克, 或安慰剂, 分别; 利伐沙班分别有 58%、75%、67%、100% 和 13% 的受试者接受 ciraparantag 30 mg、60 mg、120 mg、180 mg 或安慰剂。与 ciraparantag 相关的不良事件是轻度、短暂的潮热或潮红。结论 Ciraparantag 提供了一种剂量相关的逆转阿哌沙班或利伐沙班稳态给药诱导的抗凝作用。阿哌沙班 60 mg ciraparantag 和利伐沙班 180 mg ciraparantag 实现了持续逆转。所有剂量的 ciraparantag 均耐受良好。