%0 Journal Article
%T Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion
%A Anthony J. Comerota
%A Kecia L. Courtney
%A Kim Hanna
%A Lazar Davidovic
%A Richard D. Shlansky-Goldberg
%J Journal of Drug Assessment
%D 2019
%R https://doi.org/10.1080/21556660.2019.1586402
%X Abstract 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: NCT0122211
%U https://www.tandfonline.com/doi/full/10.1080/21556660.2019.1586402