title: Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial.
abstract: BACKGROUND
  Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents.
  
  
  METHODS
  TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment.
  
  
  CONCLUSIONS
  TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. dmorrow@partners.org
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Gail
authors.initials: G
authors.lastname: Berman
authors.forename: John
authors.initials: J
authors.lastname: Strony
authors.forename: Enrico
authors.initials: E
authors.lastname: Veltri
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.forename: Polly
authors.initials: P
authors.lastname: Fish
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: McCabe
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000188:drug therapy / Q000517:prevention & control*; D004311:Double-Blind Method; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar