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Randomized, placebo-controlled, dose-ranging clinical trial of intravenous microplasmin in patients with acute ischemic stroke

Thijs, VNS, Peeters, Anna, Vosko, M, Aichner, F, Schellinger, PD, Schneider, D, Neumann-Haefelin, T, Röther, J, Davalos, A, Wahlgren, N and Verhamme, P 2009, Randomized, placebo-controlled, dose-ranging clinical trial of intravenous microplasmin in patients with acute ischemic stroke, Stroke, vol. 40, no. 12, pp. 3789-3795, doi: 10.1161/STROKEAHA.109.560201.


Title Randomized, placebo-controlled, dose-ranging clinical trial of intravenous microplasmin in patients with acute ischemic stroke
Author(s) Thijs, VNS
Peeters, AnnaORCID iD for Peeters, Anna orcid.org/0000-0003-4340-9132
Vosko, M
Aichner, F
Schellinger, PD
Schneider, D
Neumann-Haefelin, T
Röther, J
Davalos, A
Wahlgren, N
Verhamme, P
Journal name Stroke
Volume number 40
Issue number 12
Start page 3789
End page 3795
Total pages 7
Publisher Ovid Technologies (Wolters Kluwer Health)
Place of publication United States
Publication date 2009-12-01
ISSN 0039-2499
1524-4628
Summary Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods— In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical efficacy. Results— Microplasmin induced reversible effects on markers of systemic thrombolysis and neutralized α 2 -antiplasmin by up to 80%. It was well tolerated with one of 30 treated patients developing a fatal symptomatic intracerebral hemorrhage. No significant effect on reperfusion rate or on clinical outcome was observed. Matrix metalloproteinase-2 levels were reduced in microplasmin-treated patients. Conclusions— Microplasmin was well tolerated and achieved neutralization of α 2 -antiplasmin. Further studies are warranted to determine whether microplasmin is an effective therapeutic agent for ischemic stroke.
Language en
DOI 10.1161/STROKEAHA.109.560201
Field of Research 1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
1109 Neurosciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30152657

Document type: Journal Article
Collections: Faculty of Health
PVC's Office - Health
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.