Reduced Volume and Faster Infusion Rate of Activated Prothrombin Complex Concentrate: A Phase 3b/4 Trial in Adults with Hemophilia A with Inhibitors.

Bülent Zülfikar, Johnny Mahlangu, Salim Mohamed Nekkal, Cecil Ross, Noppacharn Uaprasert, Jerzy Windyga, Carmen Escuriola Ettingshausen, Bettina Ploder, Aurelia Lelli, Hanna T Gazda
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Abstract

Background  Activated prothrombin complex concentrate (aPCC) is indicated for bleed treatment and prevention in patients with hemophilia with inhibitors. The safety and tolerability of intravenous aPCC at a reduced volume and faster infusion rates were evaluated. Methods  This multicenter, open-label trial (NCT02764489) enrolled adults with hemophilia A with inhibitors. In part 1, patients were randomized to receive three infusions of aPCC (85 ± 15 U/kg) at 2 U/kg/min (the approved standard rate at the time of the study), in a regular or 50% reduced volume, and were then crossed over to receive three infusions in the alternative volume. In part 2, patients received three sequential infusions of aPCC in a 50% reduced volume at 4 U/kg/min and then at 10 U/kg/min. Primary outcome measures included the incidence of adverse events (AEs), allergic-type hypersensitivity reactions (AHRs), infusion-site reactions (ISRs), and thromboembolic events. Results  Of the 45 patients enrolled, 33 received aPCC in part 1 and 30 in part 2. In part 1, 24.2 and 23.3% of patients with regular and reduced volumes experienced AEs, respectively; 11 AEs in eight patients were treatment related. AHRs and ISRs occurred in four (12.1%) and two (6.1%) patients, respectively. In part 2, 3.3 and 14.3% of patients with infusion rates of 4 and 10 U/kg/min experienced AEs, respectively; only one AE in one patient was treatment related; no AHRs or ISRs were reported. Most AEs were mild/moderate in severity. Overall, no thromboembolic events were reported. Conclusions  aPCC was well tolerated at a reduced volume and faster infusion rates, with safety profiles comparable to the approved regimen.

减少活性凝血酶原复合物浓缩物的用量并加快其输注速度:成人 A 型血友病患者与抑制剂的 3b/4 期试验。
背景 活化凝血酶原复合物浓缩物(aPCC)适用于治疗和预防血友病伴抑制剂患者的出血。本研究评估了静脉注射凝血酶原复合物浓缩液的安全性和耐受性。方法 这项多中心、开放标签试验(NCT02764489)招募了患有抑制剂的成人 A 型血友病患者。在第 1 部分中,患者被随机分配以 2 U/kg/min(研究时批准的标准输注速度)的速度输注三次 aPCC(85 ± 15 U/kg),输注容量为常规容量或减少 50%,然后被交叉分配以替代容量输注三次。在第 2 部分中,患者先以 4 U/kg/min 的速度,然后以 10 U/kg/min的速度,以减少 50%的容量连续输注三次 aPCC。主要结果指标包括不良事件(AEs)、过敏型超敏反应(AHRs)、输液部位反应(ISRs)和血栓栓塞事件的发生率。结果 在入组的 45 名患者中,33 人在第一部分接受了 aPCC 治疗,30 人在第二部分接受了 aPCC 治疗。在第 1 部分中,24.2% 和 23.3% 的常规量和减量患者出现了 AE;8 名患者中的 11 例 AE 与治疗有关。分别有 4 名(12.1%)和 2 名(6.1%)患者出现 AHR 和 ISR。在第 2 部分中,输注速率为 4 U/kg/min和 10 U/kg/min的患者中分别有 3.3% 和 14.3% 出现了 AE;只有一名患者的 AE 与治疗相关;没有 AHR 或 ISR 的报告。大多数 AE 的严重程度为轻度/中度。总体而言,未报告血栓栓塞事件。结论 aPCC 在输注量减少和输注速度加快的情况下耐受性良好,其安全性与已获批准的治疗方案相当。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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