THROMBOLYSIS IN MYOCARDIAL ISCHEMIA-CLINICAL APPLICATION

申请人是一组22个临床单位（45家医院），5 核心实验室和一个数据协调中心，其中大部分 参与TIMI和TIMI II研究，其长期 目的是解决目前存在争议的主要问题， 使不稳定型心绞痛患者的管理复杂化， 非Q波心肌梗死 拟议的研究，题为“血栓溶解， 心肌缺血”（TIMI III），将利用获得的专业知识 在申请人之前使用t-PA和PTCA治疗Q波MI的研究中， 确定这些新方法的价值， 不稳定型心绞痛和非Q波心肌梗死-- 每年约有100万人受到影响 美国的 该小组将进行2项随机、设盲研究（TIMI IIIA和 IIIB）针对两个具体目标：（1）确定是否t-PA 改善血管造影确定的心肌 灌注或冠状动脉狭窄（TIMI IIIA）;以及（2）识别 最佳初始和随访管理策略（TIMI IIIB）。 最初，肝素、t-PA和/或t-PA加肝素是否优于上级 在常规治疗中加入安慰剂 在后续行动中， 如果解剖结构是 合适的，通过血运重建？ TIMI IIIA将由一组13个临床单位进行， 将在9个月内随机抽取300名患者。 的影响 t-PA对血管造影测定的冠状动脉血流量的影响， 狭窄将由定量的核心实验室确定。 动脉造影 TIMI IIIB将由21个临床单位进行， 将在2年内随机抽取2,000名患者 成功 治疗的效果将由不接受治疗的患者数量来判断。 发生死亡、MI、致残性卒中或治疗失败 （定义为静息时显著复发性缺血性疼痛，或 霍尔特监测或ETT结果不满意， 铊）。 ECG/ETT分析的核心实验室，定性 血管造影、动态ECG和放射性核素（铊）研究 将确保数据收集的质量， 关键终点数据的盲态分析。 样品将是 足够的规模，以明确确定风险与收益 肝素治疗、t-PA治疗和t-PA加肝素治疗， 以及常规血管造影的价值， 对于这些严重和常见的疾病，进行血运重建。

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.