![]() The primary objective was to compare the mortality of subjects 30 days after treatment. Subjects with an AMI within 6 hours of symptom onset were eligible for this study. There was no significant difference in the rate of intracranial hemorrhage (0.9%). ![]() Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double blind randomized trial. In human clinical trials for treatment of acute myocardial infarction (AMI), tenecteplase demonstrated similar efficacy to alteplase, but major blood loss was reduced by 22%, need for blood transfusion was reduced by 23%, and minor bleeding decreased by 16% (Assessment of the Safety and Efficacy of a New Thrombolytic Investigators (ASSENT-2). In pre-clinical studies, tenecteplase has demonstrated increased potency, higher fibrin specificity, resistance to plasminogen activator inhibitor (PAI-1), and faster clot lysis, with less systemic fibrinolysis, plasminogenemia, and bleeding compared to alteplase (Refino et al., Thromb. Tenecteplase has the same mechanism of action as alteplase and has been shown to be potent and effective in promoting clot lysis in vitro (Refino et al., Thromb Haemost, 69(6):841 (1993) Keyt et al. This initiates local proteolysis of fibrin associated with the thrombus with limited proteolysis of systemic fibrinogen. Tenecteplase binds to fibrin in a thrombus and converts plasminogen to plasmin. Tenecteplase is a serine protease that converts plasminogen to plasmin in the presence of fibrin, with limited conversion of plasminogen to plasmin in the absence of fibrin. The modifications yielded a molecule with amino acid substitutions at three sites: the substitution of asparagine for threonine 103, the substitution of glutamine for asparagine 117, and a tetra-alanine substitution at amino acids 296-299 (lysine, histidine, arginine, and arginine). Tenecteplase (TNK, TNKASE™, Genentech, Inc., South San Francisco, Calif.), a tissue-plasminogen activator, is a sterile, purified glycoprotein of 527 amino acids resulting from modifications of the complementary DNA for natural human tissue plasminogen activator. More recently, a pilot study of reteplase employed for thrombolysis of deep venous thrombosis reported a major complication rate of 4% (Castaneda et al., supra). Initial results of reteplase in the treatment of acute lower extremity arterial occlusions showed a mortality rate of 6% with a currently employed low-dose regimen of 0.5 u/hour (Davidian et al., J. A tPA trial at a dose of 0.04 mg/kg/hr found major complications of 13% (Arepally et al., J. Med., 109: 52-58 (2000) for an overview of third-generation thrombolytic drugs in general.Īn early review of the literature suggested that the major complication rate undergoing thrombolysis with recombinant tissue-plasminogen activator (tPA) for peripheral arterial occlusive disease was 5.1% (Semba et al., J. ![]() Techniques have been refined and treatment of deep vein thrombosis (DVT) has been reported to be effective and safe with all available plasminogen activators in non-randomized, non-controlled observational studies (Elsharawy and Elzayat, Eur. In the past three years, significant clinical research has been performed with use of recombinantly derived agents for catheter-directed therapy (CDT). Plasmin is an active serine proteinase that degrades various proteins, including fibrin.Ĭurrently, five plasminogen activators are approved in the United States for treating coronary thromboses, but none are FDA-approved for catheter-directed thrombolysis. ![]() Plasminogen activators are enzymes that cleave the peptide bond of plasminogen between amino acid residues 561 and 562, converting it to plasmin. This invention relates to the use of a tissue-plasminogen activator variant for restoring function in dysfunctional hemodialysis catheters. ![]()
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