PMID- 31069128
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2155-6660 (Print)
IS  - 2155-6660 (Electronic)
IS  - 2155-6660 (Linking)
VI  - 8
IP  - 1
DP  - 2019
TI  - Phase 2, randomized, open-label study on catheter-directed thrombolysis with 
      plasmin versus rtPA and placebo in acute peripheral arterial occlusion.
PG  - 43-54
LID - 10.1080/21556660.2019.1586402 [doi]
AB  - 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.
FAU - Comerota, Anthony J
AU  - Comerota AJ
AD  - Medical Director Eastern Region, Inova Heart and Vascular Institute, Inova 
      Alexandria Hospital, Alexandria, VA, USA.
FAU - Davidovic, Lazar
AU  - Davidovic L
AD  - Faculty of Medicine, University of Belgrade, Clinic for Vascular and Endovascular 
      Surgery, Serbian Clinical Center, Belgrade, Serbia.
FAU - Hanna, Kim
AU  - Hanna K
AD  - Department of Clinical Development, Grifols Inc, Research Triangle Park, NC, USA.
FAU - Courtney, Kecia L
AU  - Courtney KL
AD  - Department of Clinical Development, Grifols Inc, Research Triangle Park, NC, USA.
FAU - Shlansky-Goldberg, Richard D
AU  - Shlansky-Goldberg RD
AD  - Department of Radiology, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, PA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01222117
PT  - Journal Article
DEP - 20190409
PL  - England
TA  - J Drug Assess
JT  - Journal of drug assessment
JID - 101672979
PMC - PMC6493290
OTO - NOTNLM
OT  - Arterial occlusive disease
OT  - ischemia
OT  - peripheral arterial disease
OT  - plasmin
OT  - thrombolytic therapy
EDAT- 2019/05/10 06:00
MHDA- 2019/05/10 06:01
PMCR- 2019/01/01
CRDT- 2019/05/10 06:00
PHST- 2018/08/03 00:00 [received]
PHST- 2019/02/21 00:00 [accepted]
PHST- 2019/05/10 06:00 [entrez]
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2019/05/10 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 1586402 [pii]
AID - 10.1080/21556660.2019.1586402 [doi]
PST - epublish
SO  - J Drug Assess. 2019 Apr 9;8(1):43-54. doi: 10.1080/21556660.2019.1586402. 
      eCollection 2019.