PH III: AZIMILIDE CONTROLLED TRIAL

目的：本研究的目的是评价长期使用阿奇米特治疗房颤/扑动和/或阵发性室性心动过速的安全性。心房颤动是临床上最常见的持续性心动过速的原因，75岁以上的人中有高达12%的人会发生这种情况。发病率随着生命每十年的增长而增加。此外，高达三分之一的血栓栓塞性中风是由房颤引起的。抗凝、对室性反应的药理控制和抗心律失常药物治疗一直是房颤治疗的主要手段。然而，现有的抗心律失常药物的选择及其疗效有限。具体地说，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。房颤最常与瓣膜病、缺血性心脏病或肥厚性心脏病有关，限制了可用的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性药物，限制了它们在临床上也经常发生的房颤合并窦房结疾病(慢-快综合征)患者中的应用。因此，有必要开发具有以下特点的新型抗心律失常药物：1)结构性心脏病患者的安全性。(2)无显著的负变时效应。其中一种药物是阿齐米利德，这是一种III类抗心律失常药物，在测试剂量水平上具有非常弱的心动过缓作用，在用于结构性心脏病患者时似乎是安全的。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，研究每日口服盐酸阿齐米特125 mg。结果：阿齐米特的双盲试验结果已初步报道(n=89)，结果显示，与对照组(17天，p(对数等级)为0.002)相比，阿齐米特治疗组房颤复发的平均时间(130d；100 mg/d和125 mg/d)显著缩短。意义：这项临床研究计划的意义在于检验这种有前景的抗心律失常新药在治疗房颤方面的安全性和有效性。心房颤动是临床上最常见的持续性心动过速的原因，75岁以上的人中有高达12%的人会发生这种情况。发病率随着生命每十年的增长而增加。此外，高达三分之一的血栓栓塞性中风是由房颤引起的。未来计划：Azimilide的第三阶段试验正在进行中，预计将对目前登记的患者进行总共24个月的前瞻性跟踪。在阿齐米特治疗房颤的第三阶段试验完成后，可以预见在特定的临床情况下，这种新型抗心律失常药物控制阵发性房颤的安全性和有效性将得到进一步的研究。这些研究将在不同的方案下进行。

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.