A Prospective , Randomized , Double-Blind Multicenter Trial of a Single Bolus Injection of the Novel Modified tPA E 6010 in the Treatment of Acute Myocardial Infarction : Comparison With Native t -

Objectives. This prospective, randomized, double-blind multicenter trial evaluated the efficacy and safety of a single bolus injection of the novel modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute myocardial infarction compared with that of native t-PA. Background. E6010 is a novel modified t-PA with a prolonged half-life (t1/2 alpha >223 min) compared with native t-PA (t1/2 alpha 5 4 min). E6010 can be administered in patients as a single intravenous bolus injection, and early recanalization can be expected. Methods. The efficacy of E6010 was compared with that of native t-PA in 199 patients with acute myocardial infarction who were treated within 6 h of onset in a prospective, randomized, double-blind multicenter trial. Patients were given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t-PA (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2 min, the remainder infused over 60 min). Results. The primary end point was the recanalization rate of the infarct-related coronary artery at 60 min after the start of treatment. Time to reperfusion was shorter in the E6010 group than in the native t-PA group. Thrombolysis in Myocardial Infarction flow grade 2 or 3 recanalization at 15, 30, 45 and 60 min after administration was observed in 37%, 62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated patients, respectively (p 5 0.032 at 60 min). Conclusions. The present study indicates that, compared with native t-PA, a single bolus injection of E6010 over 2 min produces a higher rate of early recanalization of the infarct-related coronary artery without fatal bleeding complications. (J Am Coll Cardiol 1997;29:1447–53) ©1997 by the American College of Cardiology

[1]  J. Kalbfleisch,et al.  More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators. , 1995, Circulation.

[2]  K. Takazawa,et al.  Phase I Study of the Modified Tissue Plasminogen Activator E 6010 , 1994 .

[3]  C. Kawai,et al.  Intracoronary Infusion of E6010 Has More Potent Thrombolytic Activity Than Tissue Plasminogen Activator (t-PA) in Dogs: A Higher Plasma Level of E6010 Than t-PA Causes Potent Thrombolytic Activity , 1993, Journal of cardiovascular pharmacology.

[4]  Gusto Angiographic Investigators.  The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. , 1993, The New England journal of medicine.

[5]  G. A. Murphy,et al.  Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators. , 1992, Journal of the American College of Cardiology.

[6]  C. Grines,et al.  A Prospective, Randomized Trial Comparing Combination Half‐Dose Tissue‐Type Plasminogen Activator and Streptokinase With Full-Dose Tissue‐Type Plasminogen Activator , 1991 .

[7]  R. Califf,et al.  Evaluation of Combination Thrombolytic Therapy and Timing of Cardiac Catheterization in Acute Myocardial Infarction: Results of Thrombolysis and Angioplasty in Myocardial Infarction–Phase5 Randomized Trial , 1991, Circulation.

[8]  S. Kimata,et al.  Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction--a report from the multicenter thrombolysis trial. , 1990, Japanese circulation journal.

[9]  F. Van de Werf,et al.  Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. , 1988, BMJ.

[10]  Dwight E. Peake,et al.  Thrombolysis in myocardial infarction (TIMI) trial: Phase I. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase , 1988 .

[11]  R. Califf,et al.  Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in patients with acute myocardial infarction. , 1988, Circulation.

[12]  F. Dati,et al.  Multicenter Evaluation of a Chromogenic Substrate Method for Photometric Determination of Prothrombin Time , 1987, Thrombosis and Haemostasis.

[13]  M. Mohler,et al.  D-Phe-Pro-Arg-Chloromethylketone: Its Potential Use in Inhibiting the Formation of In Vitro Artifacts in Blood Collected During Tissue-Type Plasminogen Activator Thrombolytic Therapy , 1986, Thrombosis and Haemostasis.

[14]  Gruppo Italiano per lo Studio della Soprawivenza nell'Inf Miocardico..  EFFECTIVENESS OF INTRAVENOUS THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION , 1986, The Lancet.

[15]  D. Rylatt,et al.  Measurement of Crosslinked Fibrin Degradation Products – An Immunoassay Using Monoclonal Antibodies , 1983, Thrombosis and Haemostasis.

[16]  J. W. Kennedy.  Early Thrombolysis in Acute Myocardial Infarction : Limitation of Infarct Size and Improved Survival , 2016 .

[17]  E. J. PubMed Citation,et al.  An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction , 2009 .

[18]  鈴木 豪.  Thrombolytic properties of a novel modified human tissue-type plasminogen activator (E6010) : a bolus injection of E6010 has equivalent potency of lysing young and aged canine coronary thrombi , 1995 .

[19]  C. Kawai.  Multicenter trial of a novel modified t-PA, E6010, by i.v.bolus injection in patients with acute myocardial infarction. , 1992 .

[20]  Y. Takada,et al.  Changes in various parameters of fibrinolysis in persons infused with tissue plasminogen activator: special reference to plasminogen activator inhibitor. , 1988, Thrombosis research. Supplement.

[21]  A. Forker,et al.  Intra-coronary thrombolysis in acute myocardial infarction. , 1983, The Nebraska medical journal.

[22]  G. Claeson,et al.  Methods for the Determination of Plasmin, Antiplasmin and Plasminogen by Means of the Substrate S-2251 , 1977, Thrombosis and Haemostasis.