THROMBOLYSIS IN MYOCARDIAL ISCHEMIA-CLINICAL APPLICATION

申请者是由22个临床单位(45家医院)、5个 核心实验室和数据协调中心，其中大多数 参加了TIMI I和TIMI II的研究，其长期 目标是解决当前存在重大争议的问题 使不稳定型心绞痛患者的处理复杂化 非Q波心肌梗死。这项拟议的研究题为“血栓溶解” 心肌缺血“(TIMI III)，将利用所获得的专业知识 在申请人与t-PA和PTCA治疗Q波MI的先前工作中， 确定这些新方法对相关 不稳定型心绞痛和非Q波心肌梗死的情况-- 在美国，每年约有100万人遭受痛苦 美国。 该小组将进行2项随机、盲法研究(TIMI IIIA和 IIIB)针对两个具体目标：(1)确定t-PA是否 改善血管造影术确定的心肌 灌注或冠状动脉狭窄(TIMI IIIA)；以及，(2)识别 最佳初始和后续管理战略(TIMI IIIB)。 最初，肝素、t-PA和/或t-PA加肝素优于 在常规治疗的基础上加用安慰剂？在后续行动中，IS 接下来有必要进行常规血管造影术，如果解剖结构 合适，通过血运重建？ TIMI IIIA将由13个临床单位组成的小组进行 将在9个月内随机抽取300名患者。的影响 血浆纤溶酶原激活物对冠脉血流和冠状动脉血流的影响 狭窄将由量化的核心实验室确定 血管造影术。TIMI IIIB将由21个临床单位进行， 这将在两年内随机抽取2000名患者。成功 治疗的效果将根据不接受治疗的患者的数量来判断 经历死亡、心肌梗死、致残性中风或治疗失败 (定义为显著的复发性静息缺血性疼痛，或 Holter监测或ETT的结果不满意 铊)。心电/ETT分析核心实验室，定性 血管造影术、动态心电图和放射性核素(铊)研究 将确保数据收集的质量，并提供集中的、 对关键终端数据进行盲目分析。样品将是 足够大的规模来清楚地确定以下各项的风险和好处 肝素治疗、t-PA治疗和t-PA加肝素治疗，AS 以及常规血管造影术的价值 血管重建术，用于这些严重和频繁的疾病。

The applicants are a group of 22 clinical units (45 hospitals), 5 core laboratories, and a data coordinating center, most of whom participated in the TIMI I and TIMI II studies, whose long-term objective is to resolve the major controversial issues currently complicating the management of patients with unstable angina and non-Q-wave MI. The proposed study, entitled "Thrompolysis in Myocardial Ischemia" (TIMI III), will utilize the expertise gained in the applicants' prior work with t-PA and PTCA for Q-wave MI, to determine the value of these new approaches for the related conditions of unstable angina and non-Q-wave MI--disorders which afflict approximately one million individuals annually in the United States. The group will conduct 2 randomized, blinded studies (TIMI IIIA and IIIB) directed toward two specific aims: (1) To determine if t-PA produces improvement in angiographically determined myocardial perfusion or coronary stenosis (TIMI IIIA); and, (2) to identify the optimal initial and follow-up management strategy (TIMI IIIB). Initially, is heparin, t-PA and/or t-PA plus heparin superior to the addition of placebo to conventional therapy? In follow-up, is there a need for routine angiography followed, if the anatomy is suitable, by revascularization? TIMI IIIA will be conducted by a group of 13 clinical units which will randomize 300 patients over a 9-month period. The effect of t-PA on angiographically determined coronary artery blood flow and stenosis will be determined by a Core Laboratory of Quantitative Angiography. TIMI IIIB will be conducted by 21 clinical units, which will randomize 2,000 patients over a 2-year period. Success of therapy will be judged by the number of patients who do not experience death, MI, disabling stroke, or failure of therapy (defined as significant recurrent ischemic pain at rest, or unsatisfactory results of Holter monitoring or an ETT with thallium). Core Laboratories for ECG/ETT analysis, qualitative angiography, ambulatory ECG, and radionuclide (thallium) studies will assure quality of data collection and provide centralized, blinded analysis of crucial endpoint data. The sample will be of sufficient size to establish clearly the risks versus benefits of heparin therapy, t-PA therapy and t-PA plus heparin therapy, as well as the value of routine angiography followed by revascularization, for these serious and frequent disorders.