title: Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: a double-blind, randomized angiographic trial of lanoteplase versus alteplase.
abstract: BACKGROUND
  Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase.
  
  
  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.affiliation: University Hospital Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: den Heijer
authors.forename: F
authors.initials: F
authors.lastname: Vermeer
authors.forename: E
authors.initials: E
authors.lastname: Ambrosioni
authors.forename: Z
authors.initials: Z
authors.lastname: Sadowski
authors.forename: J L
authors.initials: JL
authors.lastname: López-Sendón
authors.forename: R
authors.initials: R
authors.lastname: von Essen
authors.forename: P
authors.initials: P
authors.lastname: Beaufils
authors.forename: U
authors.initials: U
authors.lastname: Thadani
authors.forename: J
authors.initials: J
authors.lastname: Adgey
authors.forename: L
authors.initials: L
authors.lastname: Pierard
authors.forename: J
authors.initials: J
authors.lastname: Brinker
authors.forename: R F
authors.initials: RF
authors.lastname: Davies
authors.forename: R W
authors.initials: RW
authors.lastname: Smalling
authors.forename: L
authors.initials: L
authors.lastname: Wallentin
authors.forename: A
authors.initials: A
authors.lastname: Caspi
authors.forename: A
authors.initials: A
authors.lastname: Pangerl
authors.forename: L
authors.initials: L
authors.lastname: Trickett
authors.forename: C
authors.initials: C
authors.lastname: Hauck
authors.forename: D
authors.initials: D
authors.lastname: Henry
authors.forename: P
authors.initials: P
authors.lastname: Chew
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator