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Katrin Voelter, Christoph Tappeiner, Karina Klein, Nicole Borel, Deborah Bruetsch, Fernando Laguna Sanz, Simon Anton Pot
PURPOSE: Desmoteplase (DSPA) was evaluated and compared with tissue plasminogen activator (t-PA) for its intraocular fibrinolytic effect and short-term toxicity in an in vivo study using rabbit eyes. METHODS: Fibrin clots were induced in the anterior chamber of 44 rabbit eyes, and drug efficacy was measured by clot size reduction over 24 h. Topical DSPA eye drops (1.4 and 2 mg/mL) were compared with vehicle solution in a multiple-drop regimen in 8 animals per group...
October 30, 2018: Journal of Ocular Pharmacology and Therapeutics
Xiaoqiang Li, Li Ling, Chuqiao Li, Qiujie Ma
BACKGROUND: Pending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain undetermined. The aim of this meta-analysis was to help evaluate desmoteplase's efficacy and safety. METHODS: A thorough search was performed of the Cochrane Library, PubMed, and Embase from the inception of electronic data to March 2017, and double-blind, multicenter, parallel-group, randomized trials were chosen...
May 2017: Medicine (Baltimore)
Ahmed Elmaraezy, Abdelrahman Ibrahim Abushouk, Soha Saad, Moutaz Eltoomy, Osama Mahmoud, Hossam Mahmoud Hassan, Ahmed Aboelmakarem, Ahmed Aboel Fotoh, Farah Althaher, Nguyen Tien Huy, Kenji Hirayama
INTRODUCTION: There is an unmet need to develop better treatments for acute ischemic stroke (AIS). Desmoteplase is a vampire bat saliva-derived analogue of human tissue plasminogen activator. It has higher fibrin selectivity and a longer half-life, compared to alteplase. We performed this metaanalysis to investigate the safety and efficacy of desmoteplase in AIS. METHOD: A computer literature search (PubMed, EMBASE, CENTRAL, Scopus, Web of science, and clinicaltrials...
2017: CNS & Neurological Disorders Drug Targets
Rüdiger von Kummer, Etsuro Mori, Thomas Truelsen, Jens-Kristian S Jensen, Bjørn A Grønning, Jochen B Fiebach, Karl-Olof Lovblad, Salvador Pedraza, Javier M Romero, Hugues Chabriat, Ku-Chou Chang, Antoni Dávalos, Gary A Ford, James Grotta, Markku Kaste, Lee H Schwamm, Ashfaq Shuaib, Gregory W Albers
BACKGROUND AND PURPOSE: The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window...
December 2016: Stroke; a Journal of Cerebral Circulation
Florian C Roessler, Sabrina Schumacher, Andreas Sprenger, Ulrich Gärtner, Mohamed Al-Khaled, Jürgen Eggers
BACKGROUND: Patients with acute ischemic strokes frequently take an acetylsalicylic acid (ASA) premedication. We determined the impact of ASA on different thrombolysis strategies in vitro. METHODS: For two clot types made from platelet-rich plasma (one with and one without ASA) lysis rates were measured by weight loss after 1 h for five different groups: in control group A clots were solely placed in plasma; in groups B and C clots were treated with rt-PA (60 kU/ml), and in groups D and E clots were treated with desmoteplase (DSPA; 2 µg/ml)...
2016: Journal of Vascular Research
Ligen Shi, Feng Liang, Yunping Li, Anwen Shao, Keren Zhou, Jun Yu, Jianmin Zhang
Recent studies have shown inconsistent results regarding the value of desmoteplase for treating acute ischemic stroke (AIS) when administered within an extended time window. We performed a meta-analysis to explore the value of desmoteplase in AIS treatment. The MEDLINE, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that had evaluated desmoteplase versus placebo for AIS. The primary outcomes were intracranial hemorrhage (ICH) within 72 hours and favorable outcome at Day 90...
September 27, 2016: Scientific Reports
Aldo Bonaventura, Fabrizio Montecucco, Franco Dallegri
INTRODUCTION: Acute ischemic stroke (AIS) represents a major cause of death and disability all over the world. The recommended therapy aims at dissolving the clot to re-establish quickly the blood flow to the brain and reduce neuronal injury. Intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) is clinically used with this goal. AREAS COVERED: A description of beneficial and detrimental effects of rt-PA treatment is addressed. An overview of new therapies against AIS, such as new thrombolytics, sonolysis and sonothrombolysis, endovascular procedures, and association therapies is provided...
November 2016: Expert Opinion on Biological Therapy
Bruce C V Campbell
Acute ischemic stroke is responsible for around 80% of all strokes and is a leading cause of disability and death globally. There are two potential treatment strategies: restoring blood flow (reperfusion) and preventing cellular injury (neuroprotection). As yet, all the successful trials have involved reperfusion with numerous failures of neuroprotectants. There are two proven reperfusion strategies. Intravenous thrombolysis with alteplase was first demonstrated to reduce disability with publication of the National Institute of Neurological Disorders and Stroke tissue plasminogen activator trial in 1995...
March 2017: Seminars in Thrombosis and Hemostasis
Perttu J Lindsberg, Valeria Caso
No abstract text is available yet for this article.
March 2016: Stroke; a Journal of Cerebral Circulation
Nicola Logallo, Christopher E Kvistad, Aliona Nacu, Lars Thomassen
Progress in finding a better alternative to alteplase has been slow. Tenecteplase and desmoteplase have better pharmacological profiles compared with alteplase, but definite clinical evidence of their superiority is lacking. The two major phase III studies that have tested the efficacy and safety of desmoteplase in ischemic stroke patients have shown neutral results and a promising safety profile, but the trials compared desmoteplase with placebo only in late admitted patients. Future trials should focus on testing novel thrombolytics in the early time window either as the sole acute recanalizing treatment or combined with thrombectomy...
February 2016: CNS Drugs
C Paris, L Derex
New therapeutic strategies are under evaluation to improve the treatment of acute ischemic stroke (AIS). Approaches combining intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) and antithrombotic agents are currently evaluated. The combination of IV rt-PA and aspirin showed a high rate of intracranial hemorrhage whereas the association of rt-PA and eptifibatide seems more promising. The results of recent studies evaluating the administration of eptifibatide or argatroban in conjunction with conventional IV thrombolysis with rt-PA are expected to clarify the safety and efficacy of these treatments...
December 2015: Revue Neurologique
Florian C Roessler, Zhihua Wang, Sabrina Schumacher, Marcus Ohlrich, Manfred Kaps, Arianna Menciassi, Jürgen Eggers
The aim of the study described here was to evaluate the thrombolytic efficacy of combined treatment with the fibrin-selective plasminogen activator desmoteplase (DSPA) and therapeutic ultrasound (sonothrombolysis [STL]) compared with conventional rt-PA (recombinant tissue plasminogen activator) treatment in vitro. Lysis rates were determined by the weight loss of platelet-rich plasma (PRP) clots treated with rt-PA (60 kU/mL) or DSPA (2 μg/mL) combined with pulsed wave ultrasound (2 MHz, 0.179 W/cm(2)). To reveal the individual effects of medication and ultrasound, lysis rates were also determined for DSPA monotherapy and for combined treatment with rt-PA and ultrasound...
December 2015: Ultrasound in Medicine & Biology
Etsuro Mori, Kazuo Minematsu, Jyoji Nakagawara, Yasuhiro Hasegawa, Shinji Nagahiro, Yasushi Okada, Thomas Truelsen, Annika Lindsten, Akira Ogawa, Takenori Yamaguchi
BACKGROUND AND PURPOSE: This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke. METHODS: Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 μg/kg and then 90 μg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography...
September 2015: Stroke; a Journal of Cerebral Circulation
Gregory W Albers, Rüdiger von Kummer, Thomas Truelsen, Jens-Kristian S Jensen, Gabriela M Ravn, Bjørn A Grønning, Hugues Chabriat, Ku-Chou Chang, Antonio E Davalos, Gary A Ford, James Grotta, Markku Kaste, Lee H Schwamm, Ashfaq Shuaib
BACKGROUND: Current treatment of ischaemic stroke with thrombolytic therapy is restricted to 3-4·5 h after symptom onset. We aimed to assess the safety and efficacy of desmoteplase, a fibrin-dependent plasminogen activator, given between 3 h and 9 h after symptom onset in patients with occlusion or high-grade stenosis in major cerebral arteries. METHODS: In a prospective, double-blind, multicentre, parallel-group, randomised trial, we enrolled patients from 77 hospitals in 17 countries who had ischaemic stroke and occlusion or high-grade stenosis in major cerebral arteries...
June 2015: Lancet Neurology
Michael D Hill, Bijoy K Menon
No abstract text is available yet for this article.
June 2015: Lancet Neurology
H Asadi, B Yan, R Dowling, S Wong, P Mitchell
Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase...
2014: Thrombosis
Georgios Tsivgoulis, Aristeidis H Katsanos, Andrei V Alexandrov
Over the past 20 years, clinical research has focused on the development of reperfusion therapies for acute ischemic stroke (AIS), which include the use of systemic intravenous thrombolytics (alteplase, desmoteplase, or tenecteplase), the augmentation of systemic intravenous recanalization with ultrasound, the bridging of intravenous with intra-arterial thrombolysis, the use of multi-modal approaches to reperfusion including thrombectomy and thromboaspiration with different available retrievers. Clinical trials testing these acute reperfusion therapies provided novel insight regarding the comparative safety and efficacy, but also raised new questions and further uncertainty on the field...
2014: Frontiers in Neurology
Amirhossein Saadatirad, Soroush Sardari, Mohammadreza Kazemali, Najmeh Zarei, Fatemeh Davami, Farzaneh Barkhordari, Ahmad Adeli, Fereidoun Mahboudi
Thrombolytic therapy by plasminogen activators (PAs) has been a main goal in the treatment of acute myocardial infarction. Despite improved outcomes of currently available thrombolytic therapies, all these agents have different drawbacks that may result in less than optimal outcomes. In order to make tissue plasminogen activator (tPA) more potent, while being more resistant to plasminogen activator inhibitor-1 (PAI-1) and having a higher affinity to fibrin, a new chimeric-truncated form of tPA (CT tPA) was designed and expressed in Pichia pastoris...
December 2014: Molecular Biotechnology
Joanna M Wardlaw, Veronica Murray, Eivind Berge, Gregory J del Zoppo
BACKGROUND: Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA...
July 29, 2014: Cochrane Database of Systematic Reviews
Essam Kotb
Formation of endogenous thrombi in blood vessels is one of the leading causes of death in our modern life. According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world. For this, a tremendous amount of research has been done in the area of prevention and treatment of these diseases. The classical therapy of these thrombi relies upon the use of antiplatelets, anticoagulants, or even surgeries. Relatively recently, the fibrinolytic enzymes produced by microorganisms, snakes, earthworms, insects, plants, and other organisms are being successfully used in the treatment of blood clots, especially with regard to the direct dissolving action on fibrin in tandem with less cost and side effects in comparison with the first-generation thrombolytic agents, streptokinase and urokinase...
May 2014: Biotechnology Progress
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