THROMBOLYSIS IN MYOCARDIAL ISCHEMIA-CLINICAL APPLICATION

心肌缺血中的溶栓临床应用

• 批准号: 3360421
• 负责人: EUGENE BRAUNWALD
• 金额: $ 5.58万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-02-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3360421
• 关键词: angiocardiography; electrocardiography; fibrinolytic therapy; heart disorder chemotherapy; heart imaging /visualization /scanning; heart revascularization; heparin; home health care; human subject; human therapy evaluation; myocardial ischemia /hypoxia; plasminogen activator; radionuclide imaging /scanning

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.

申请人为22家临床单位（45家医院）、5家 核心实验室和数据协调中心，其中大部分 参与了TIMI I和TIMI II研究，其长期 目的是解决当前存在的重大争议问题 使不稳定心绞痛患者的治疗变得复杂化 非Q波MI。 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 进行 Q-wave MI 的工作中， 确定这些新方法对相关领域的价值 不稳定型心绞痛和非 Q 波 MI 疾病 每年影响大约一百万人 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策略（TIMI IIIB）。 最初，肝素、t-PA 和/或 t-PA 加肝素优于 在常规治疗中添加安慰剂？ 后续，是 如果解剖结构符合，则需要进行常规血管造影 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 个月内对 300 名患者进行随机分组。 的效果 t-PA 对血管造影确定的冠状动脉血流量和 狭窄程度将由定量核心实验室确定 血管造影。 TIMI IIIB将由21个临床单位进行， 它将在 2 年内对 2,000 名患者进行随机分组。 成功 治疗的效果将根据不接受治疗的患者数量来判断 经历死亡、心肌梗死、致残性中风或治疗失败 （定义为休息时明显的复发性缺血性疼痛，或 Holter 监测或 ETT 的结果不令人满意 铊）。 ECG/ETT 定性分析核心实验室 血管造影、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、 对关键终点数据进行盲法分析。 样本将是 足够的规模来清楚地确定风险与收益 肝素治疗、t-PA 治疗和 t-PA 加肝素治疗，如 以及常规血管造影的价值 血运重建，用于治疗这些严重且常见的疾病。