TIMI12--ORAL PLATELET GPIIB/IIIA ANTAGONIST IN POST ACUTE CORONARY SYNDROME

抗血栓治疗在治疗和预防中发挥着重要作用。 心肌梗死和不稳定型心绞痛统称为急性 冠脉综合征(ACS)。抗血栓治疗，如果当时存在 斑块破裂(即阿司匹林)或在服用阿司匹林时急性给药 临床事件(如阿司匹林或肝素)可以限制或部分预防 局部血栓形成从进展到完全闭塞(即 MI)。在几天或几周的时间里，抗血栓治疗可以 内源性纤溶作用可溶解急性血栓形成，使 钝化病变，并将急性病变恢复到稳定 斑块。 比阿司匹林更有效的抗血小板药物现已面市； 这些药物是血小板膜糖蛋白IIb/IIIa(GP)的拮抗剂 IIB/IIIA)。GP IIb/IIIa是血小板纤维蛋白原受体，在 在血小板聚集中的重要作用。GP IIb/IIIa拮抗剂完成 与纤维蛋白原结合以与GP IIb/IIIa结合从而干扰 血小板聚集。 口服GP IIb/IIIa拮抗剂Ro 48-3657(也称为G7333)已被 由F.Hoffman-LaRoche Ltd.和Genentech，Inc.的科学家开发 提供了长期门诊治疗的潜力。 这项名为TIMI 12的第二阶段研究的目标是确定剂量 将实现对ADP的高度和中等程度抑制的方案- 诱导急性冠脉综合征患者的血小板聚集，并测定 如果这些剂量方案是可以耐受的。 患者将在RO48-3657、ASA或安慰剂的剂量之间随机分配。 服药28天，在第7天、第14天和第28天进行随访。 第7天将进行诊所访问，第14天将进行后续电话访问 并于第28天再次住院检查血液和尿液样本以确定 剂量反应。

Antithrombotic therapy plays a major role in the treatment and prevention of MI and unstable angina which are collectively referred to as acute coronary syndromes (ACS). Antithrombotic therapy, if present at the time of a plaque rupture (i.e., aspirin) or administered acutely at the time of a clinical event (i.e., aspirin or heparin) can limit or partly prevent the local thrombosis from progressing to a complete occlusion (i.e., an MI). Over a period of daysor weeks, antithrombotic therapy allows endogenous fibrinolysis to dissolve the acute thrombosis, allows passivation of the lesion, and restores the acute lesion to a stable plaque. Antiplatelet agents that are more potent than aspirin are now available; these agents are antagonists to platelet glycoprotein IIb/IIIa (GP IIb/IIIa). GP IIb/IIIa is the platelet fibrinogen receptor and plays an essential role in platelet aggregation. GP IIb/IIIa antagonists complete with fibrinogen for binding to GP IIb/IIIa and thereby interfere with platelet aggregation. An oral GP IIb/IIIa antagonist, Ro 48-3657 (also known as G7333), has been developed by scientists at F. Hoffman-LaRoche Ltd. and Genentech, Inc. and provides the potential of long-term outpatient therapy. The goal of this Phase II study, called TIMI 12, is to identify dose regimens that will achieve high-grade and medium-grade inhibition of ADP- induced platelet aggregation in post ACS sbujects, and also to determine if these dose regimens are tolerable. Patient will be randomized between doses of Ro 48-3657, ASA, or placebo. Pills will be given bid for 28 days and followed up on day 7, 14 and 28. A clinic visit will take place on day 7, follow-up phone call on day 14 and rehospitalization on day 28 for blood and urine sample to determine dose response.