Anthony J Comerota, Lazar Davidovic, Kim Hanna, Kecia L Courtney, Richard D Shlansky-Goldberg
{"title":"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。","authors":"Anthony J Comerota, Lazar Davidovic, Kim Hanna, Kecia L Courtney, Richard D Shlansky-Goldberg","doi":"10.1080/21556660.2019.1586402","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Objectives:</b> 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. <b>Patients/methods:</b> 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. <b>Results:</b> 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 (<i>p</i> = 0.149) and 40% (2/5) for placebo control (<i>p =</i> 0.648). The thrombolytic efficacy was 33% of the 250 mg plasmin group. There was no difference (<i>p</i> > 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. <b>Conclusions:</b> 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. <b>ClinicalTrials.gov Identifier:</b> NCT01222117.</p>","PeriodicalId":15631,"journal":{"name":"Journal of Drug Assessment","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2019-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21556660.2019.1586402","citationCount":"3","resultStr":"{\"title\":\"Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion.\",\"authors\":\"Anthony J Comerota, Lazar Davidovic, Kim Hanna, Kecia L Courtney, Richard D Shlansky-Goldberg\",\"doi\":\"10.1080/21556660.2019.1586402\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> 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. <b>Objectives:</b> 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. <b>Patients/methods:</b> 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. <b>Results:</b> 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 (<i>p</i> = 0.149) and 40% (2/5) for placebo control (<i>p =</i> 0.648). The thrombolytic efficacy was 33% of the 250 mg plasmin group. There was no difference (<i>p</i> > 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. <b>Conclusions:</b> 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. <b>ClinicalTrials.gov Identifier:</b> NCT01222117.</p>\",\"PeriodicalId\":15631,\"journal\":{\"name\":\"Journal of Drug Assessment\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2019-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/21556660.2019.1586402\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Drug Assessment\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/21556660.2019.1586402\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2019/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Assessment","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21556660.2019.1586402","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
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.