PH III: AZIMILIDE CONTROLLED TRIAL

PH III：阿齐利利对照试验

• 批准号: 6415259
• 负责人: TRISTRAM D BAHNSON
• 金额: $ 29.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415259
• 关键词: antiarrhythmic agent; atrial fibrillation; clinical research; drug administration rate /duration; heart disorder chemotherapy; human subject; human therapy evaluation; imidazole; tachycardia

Purpose: The purpose of this study is to assess the safety of long-term use of azimilide in patients with atrial fibrillation/flutter and/or paroxysmal sypraventricular tachycardia. Atrial fibrillation is the most common cause of clinically significant sustained tachycardia and occurs in up to 12% of individuals over age 75. Incidence increases with each decade of life. Furthermore, atrial fibrillation is responsible for up to 1/3 of thromboembolic strokes. Anticoagulation, pharmacologic control of the ventricular response, and antiarrhythmic pharmacotherapy have been the main stays of treatment for atrial fibrillation. However, the selection of available antiarrhythmic drugs, and their efficacy, are limited. Specifically, of available antiarrhythmic agents, only sotalol and amiodarone are considered safe in patients with underlying heart disease. Atrial fibrillation is most often associated with valvular, ischemic, or hypertrophic heart disease, limiting the use of available type I antiarrhythmic agents. Further, the class III agents sotalol and amiodarone are potent negative chronotropic agents which limits their usefulness in patients with atrial fibrillation in association with sinus node disease (brady-tachy syndrome), also a frequent clinical occurence. Accordingly, there is an important need for the development of new antiarrhythmic drugs with the following characteristics: 1) safety in patients with structural heart disease. 2) absence of significant negative chronotropic effects. One such drug is Azimilide, a class III antiarrhythmic agent with very weak bradycardic effects at test dosing levels, and which appears to be safe when used in individuals with structural heart disease. Methods: This is a multi-center double-blind, placebo-controlled, parallel design clinical trial studying a daily oral dose of 125 mg of azimilide dihydrochloride. Results: Results of the double blind trial of azimilide has been reported in preliminary form (n=89) with demonstration of a significant decreases in mean time to AF recurrence in azimilide treated patients (130 days; 100mg/d and 125mg/d) comparted with control (17 days, p (log rank) of 0.002). Significance: The significance of this clinical research program is to test the safety and efficacy of this promising new antiarrhythmic drug in the treatment of atrial fibrillation. Atrial fibrillation is the most common cause of clinically significant sustained tachycardia and occurs in up to 12% of individuals over age 75. Incidence increases with each decade of life. Furthermore, atrial fibrillation is responsible for up to 1/3 of thromboembolic strokes. Future Plans: Phase III trials of Azimilide are ongoing, and it is anticipated that currently enrolled patients will be followed prospectively for a total of 24 months. After completion of the phase III trials of Azimilide for treatment of atrial fibrillation, further studies of the safety and efficacy of this new antiarrhythmic agent to control paroxysmal atrial fibrillation in specific clinical circumstances are envisioned. These studies will be conducted under separate protocol.

目的：本研究的目的是评估长期使用阿齐米利治疗心房颤动/扑动和/或阵发性室旁性心动过速的安全性。房颤是临床上显著的持续性心动过速的最常见原因，在75岁以上的个体中发生率高达12%。发病率随着年龄的增长而增加。此外，房颤是负责高达1/3的血栓栓塞性中风。抗凝、心室反应的药理学控制和抗心律失常药物治疗一直是房颤治疗的主要内容。然而，现有抗心律失常药物的选择及其疗效是有限的。具体来说，在现有的抗心律失常药物中，只有索他洛尔和胺碘酮被认为对潜在心脏病患者是安全的。房颤通常与瓣膜性、缺血性或肥厚性心脏病相关，限制了现有I型抗心律失常药物的使用。此外，III类药物索他洛尔和胺碘酮是有效的负性变时药物，这限制了它们在与窦房结疾病（心动过缓综合征）相关的心房颤动患者中的应用，窦房结疾病也是一种常见的临床疾病。因此，迫切需要开发具有以下特点的新型抗心律失常药物：1)对结构性心脏病患者安全。2)无显著负性变时效应。其中一种药物是Azimilide，这是一种III类抗心律失常药物，在试验剂量水平下具有非常弱的心动过缓作用，并且在患有结构性心脏病的个体中使用时似乎是安全的。方法：这是一项多中心、双盲、安慰剂对照、平行设计的临床试验，研究每日口服125mg盐酸阿齐米利。结果：阿齐米利德双盲试验的初步结果（n=89）显示，阿齐米利德治疗的患者（130天，100mg/d和125mg/d）与对照组（17天，p （log rank）为0.002）相比，到房间隔复发的平均时间显著缩短。意义：本临床研究项目的意义在于检验这种有前景的新型抗心律失常药物治疗心房颤动的安全性和有效性。房颤是临床上显著的持续性心动过速的最常见原因，在75岁以上的个体中发生率高达12%。发病率随着年龄的增长而增加。此外，房颤是负责高达1/3的血栓栓塞性中风。未来计划：Azimilide的III期试验正在进行中，预计目前入组的患者将被随访24个月。Azimilide治疗心房颤动的III期临床试验完成后，我们将进一步研究这种新型抗心律失常药物在特定临床情况下控制阵发性心房颤动的安全性和有效性。这些研究将按照单独的规程进行。