ANGIOTENSIN-II BLOCKADE IN MITRAL REGURGITATION

血管紧张素 II 阻断治疗二尖瓣反流

• 批准号: 6638656
• 负责人: MAURICE ENRIQUEZ-SARANO
• 金额: $ 62.95万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638656
• 关键词: ACE inhibitors; angiotensin II; angiotensin receptor; antihypertensive agents; clinical research; clinical trials; computed axial tomography; drug screening /evaluation; echocardiography; heart disorder chemotherapy; heart enlargement; human subject; human therapy evaluation; intracardiac volume; mitral valve insufficiency; patient oriented research

DESCRIPTION (the applicant's description verbatim): Background: Mitral regurgitation (MR) is frequent and its prevalence is increasing with aging of the population. Organic MR, due to primary valvular lesions has severe consequences determined by its degree, with left ventricular (LV) remodeling and dysfunction, left atrial (LA) enlargement, leading to poor clinical outcome. Surgery can eliminate MR, but carries notable risks and is not applicable to all patients. Therefore, chronically decreasing MR, protecting LV and LA with vasoactive treatment are major goals of medical therapy. However, effects of chronic oral vasoactive treatment of MR are controversial and uncertain and recent practice guidelines underscored these gaps in knowledge and did not recommend vasoactive treatment of MR. Hence, a trial of treatment of organic MR is needed. A large trial with mortality-morbidity end-points is desirable but premature without knowledge of magnitude of mechanistic effects of vasoactive treatment. Our pilot studies suggest that sustained improvement of degree of' MR, LV remodeling and LA enlargement can be achieved with tissue angiotensin blockade. The improvement of these intermediate endpoints, mechanistically linked to outcome, is measurable with non-invasive quantitative techniques and forms the basis of the present clinical trial proposal. Hypothesis: Chronic tissue angiotensin blockade therapy using either angiotensin-II receptor blocker (Candesartan Cilexetil) or tissue angiotensin-converting enzyme inhibition (Ramipril) in two arms, weighed against placebo produces a sustained reduction of the consequences of organic MR. Specific aims are that treatment improves a) degree of MR (decreases regurgitant volume, primary end-point), b) LV remodeling (decreases LV end-diastolic volume index, second end-point), and c) LA enlargement (decreases LA volume, third end-point) as compared to placebo. Population: Patients with MR organic (intrinsic valve disease), isolated (no other valve disease), equal to or greater than moderate (regurgitant volume equal to or greater than 30 mL/beat). Methods: A randomized clinical trial, placebo controlled, double-blind, without crossover, of 1 year oral treatment with potent tissue angiotensin blockade (with one arm using Candesartan and one arm using Ramipril) titrated to the maximally tolerated dose. The trial is preceded by an acute study to determine tolerance. End-points are measured by Doppler-Echocardiography for quantitation of MR (regurgitant volume) using combination of 3 simultaneous methods (quantitative Doppler, two-dimensional echocardiography, proximal flow convergence) and combination of echocardiography and electron beam computed tomography for LV and LA volume measurement. This single center study seeks to enroll a total of 135 patients. The analysis will be based on intention to treat and compare changes in regurgitant volume, LV end-diastolic volume index and LA volume measured after one year of treatment with active drugs or placebo. The results of this clinical trial should provide strong evidence regarding medical treatment of patients with organic MR and define future strategies to minimize mortality and morbidity of organic MR.

描述（申请人的描述逐字描述）：背景：二线 反流（MR）经常出现，其患病率正在增加 人口。有机MR，由于原发性瓣膜病变的严重 由左心室（LV）重塑确定的后果 和功能障碍，剩下心房（LA）扩大，导致临床不良 结果。手术可以消除MR，但具有明显的风险，而不是 适用于所有患者。因此，长期降低MR，保护LV 通过血管活性治疗的LA是医疗治疗的主要目标。然而， MR的慢性口服血管活性治疗的影响是有争议的， 不确定和最近的实践指南强调了这些知识的差距 并且不建议对MR进行血管活性治疗。因此，治疗试验 需要有机MR。死亡率终点的大型试验是 理想但过早，没有机械效应的数量 血管活性治疗。我们的试点研究表明，持续改进 可以通过组织实现MR，LV重塑和LA扩大的程度 血管紧张素阻滞。这些中间端点的改进， 机械上与结果相关，可以通过非侵入性定量来测量 技术和构成了本临床试验建议的基础。 假设：使用任何一种 血管紧张素-II受体阻滞剂（Candesartan cilexetil）或组织 血管紧张素转换酶抑制（ramipril）在两个臂上，称重 反对安慰剂会持续减少有机的后果 先生。具体目的是治疗提高了a）MR的程度（降低 反流体积，初级终点），b）LV重塑（减少LV 末期舒适音量指数，第二点）和c）扩大（减少 与安慰剂相比，LA卷，第三点）。人口：患者 有机先生（内在瓣膜疾病），分离（没有其他瓣膜疾病），相等 到或大于中等（反流量等于或大于30 ml/beat）。方法：一项随机临床试验，由安慰剂控制， 通过有效组织进行1年口服处理的双盲，没有跨界 血管紧张素封锁（用坎德萨尔坦用一只手臂和一只手臂使用一只手臂 ramipril）滴定至最大耐受剂量。试验之前 急性研究以确定公差。端点是通过 使用多普勒 - 心动摄影用于定量MR（反流量） 3种同时方法的组合（定量多普勒，二维 超声心动图，近端流融合）和组合 LV和LA体积的超声心动图和电子束计算机断层扫描 测量。这项单一中心研究旨在招募135名患者。 该分析将基于治疗和比较变化的意图 反流量，LV末端 - 舒张音量指数和LA量之后 用活跃药物或安慰剂治疗一年。结果的结果 临床试验应提供有关医学治疗的有力证据 有机MR的患者并定义了未来的策略，以最大程度地减少死亡率和 有机MR的发病率。