2期随机、开放标签研究:纤溶酶导管溶栓与rtPA和安慰剂治疗急性外周动脉闭塞。

IF 2.4 Journal of Drug Assessment Pub Date : 2019-04-09 eCollection Date: 2019-01-01 DOI:10.1080/21556660.2019.1586402
Anthony J Comerota, Lazar Davidovic, Kim Hanna, Kecia L Courtney, Richard D Shlansky-Goldberg
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引用次数: 3

摘要

背景:急性外周动脉闭塞(aPAO)患者是手术取栓、搭桥或使用纤溶酶原激活剂的导管溶栓(CDT)的候选者。人血浆源性纤溶蛋白可能提供另一种CDT选择。目的:比较重组组织型纤溶酶原激活剂(rtPA)和安慰剂在aPAO患者中两种血栓内给药方式和两种剂量的纤溶酶的疗效、安全性和耐受性。患者/方法:这是一项针对aPAO患者动脉内纤溶酶CDT的2期、随机、开放标签研究。该研究使用输液管(有或没有球囊阻塞)来评估150 mg纤溶酶(输注后2和5小时)和250 mg纤溶酶(输注后5小时)。评估纤溶酶、rtPA和安慰剂的疗效。结果:共纳入174名受试者。总体而言,不含BOC的150 mg纤溶蛋白的溶栓疗效(>50%溶栓)为59%(58/99),与不含BOC的rtPA的89% (8/9)(p = 0.149)和安慰剂对照组的40% (2/5)(p = 0.648)相当。溶栓效果为250 mg溶栓酶组的33%。两组患者溶栓疗效差异无统计学意义(p > 0.999)(59%, 58/99)。血浆纤溶酶治疗组出现治疗性不良事件(teae)的比例分别为71%(76/107)和63%(24/38)。rtpa治疗组78%(7/9)和安慰剂组89%(8/9)发生teae。150 mg纤溶酶组中有29%(31/107)发生严重不良反应,有24%(9/38)发生严重不良反应。250 mg溶酶组未发生急性脑损伤。结论:与rtPA相比,150 mg和250 mg剂量的纤溶酶在导管指导给药时出血较少。BOC的使用并没有提高疗效。CDT +纤溶酶对aPAO患者有潜在的溶栓益处。ClinicalTrials.gov标识符:NCT01222117。
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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Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion.

Background: Patients with acute peripheral arterial occlusion (aPAO) are candidates for operative thrombectomy, bypass, or catheter-directed thrombolysis (CDT) using a plasminogen activator. Human plasma-derived plasmin may offer another CDT option. Objectives: To evaluate the efficacy, safety, and tolerability of two intrathrombus delivery methods and two doses of plasmin compared with recombinant tissue plasminogen activator (rtPA) and placebo in patients with aPAO. Patients/methods: This was a phase 2, randomized, open-label study of intra-arterial CDT of plasmin in patients with aPAO. The study used infusion catheters with or without balloon occlusion (BOC) to evaluate 150 mg plasmin (2 and 5 h post-infusion) and 250 mg plasmin (5 h post-infusion). The efficacy of plasmin, rtPA and placebo was assessed. Results: One hundred and seventy-four subjects were enrolled. Overall, the thrombolytic efficacy (>50% thrombolysis) was 59% (58/99) for 150 mg plasmin without BOC, which is comparable to 89% (8/9) for rtPA without BOC (p = 0.149) and 40% (2/5) for placebo control (p = 0.648). The thrombolytic efficacy was 33% of the 250 mg plasmin group. There was no difference (p > 0.999) in thrombolytic efficacy with BOC (59%, 58/99) or without BOC (59%, 17/29). Plasmin-treated groups experienced treatment-emergent adverse events (TEAEs) at 71% (76/107) without BOC and 63% (24/38) with BOC; 78% (7/9) of the rtPA-treated group and 89% (8/9) of the placebo group had TEAEs. Serious AEs (SAEs) occurred in 29% (31/107) of the 150 mg plasmin group without BOC and 24% (9/38) with BOC. No SAEs occurred in the 250 mg plasmin group. Conclusions: Plasmin demonstrated less bleeding during catheter-directed administration at 150 mg and 250 mg doses compared to rtPA. BOC utilization did not improve efficacy. CDT with plasmin has a potential thrombolytic benefit in patients presenting with aPAO. ClinicalTrials.gov Identifier: NCT01222117.

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Journal of Drug Assessment
Journal of Drug Assessment PHARMACOLOGY & PHARMACY-
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