BACKGROUND:Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS:InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
RCT Entities:
BACKGROUND: Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS: InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
Authors: Nimish N Vachharajani; Ralph H Raymond; Wen-Chyi Shyu; Bruce C Stouffer; David W Boulton Journal: Br J Clin Pharmacol Date: 2011-11 Impact factor: 4.335
Authors: John B Kostis; Randy C Dockens; Udho Thadani; Vasnath Bethala; Carl Pepine; Wayne Leimbach; Nimish Vachharajani; Ralph H Raymond; Bruce C Stouffer; Lee K Tay; Wen Chyi Shyu; Wei-chi Liao Journal: Clin Pharmacokinet Date: 2002 Impact factor: 6.447