硫酸卡维地洛缓释胶囊治疗轻、中度原发性高血压的随机、双盲、平行对照、多中心的Ⅲ期临床药物试验

发布时间：2018-09-12 20:24

【摘要】：背景:高血压分为原发性和继发性,其中原发性高血压占整个高血压中的90%。高血压早期直接致病因素为交感神经系统活性增加,因此及早阻断交感活性,减少去甲肾上腺素的释放是治疗高血压主要机制之一,这样可及时有效的控制血压,减少并发症,减轻社会经济负担,提高高血压患者的生活质量。β受体阻滞剂能够抑制交感神经活性,对高血压的治疗有一定的效果。卡维地洛是第3代β受体阻滞剂的一种新产品,药理学作用比第1、2代受体阻滞剂更广,对α1、β1、β2受体都有阻滞作用,并具有调节儿茶酚胺对心脏、末梢血管和肾脏的不利影响,逆转血管紧张素和受体改变等的联合调节作用,而没有单纯扩血管或β受体阻滞带来的副反应,其降压效果肯定及副作用少对高血压患者来说无疑是一个重要的理想治疗药物,具有良好的临床应用前景。目的:以琥珀酸美托洛尔缓释片为对照,评价硫酸卡维地洛缓释胶囊治疗轻、中度原发性高血压的有效性和安全性;通过动态血压开放研究观察硫酸卡维地洛缓释胶囊对受试者24小时血压的控制效果。方法:对诊断为轻、中度高血压患者,进行严格筛选后入组进行硫酸卡维地洛缓释胶囊治疗轻、中度原发性高血压的随机、双盲、阳性药物平行对照、多中心的临床试验。主要分为两项:一项为多中心、随机、双盲双模拟、阳性药物平行对照临床研究,另一项为单臂、开放、多中心动态血压临床研究。分别在给药前和给药后进行血生化、血常规、尿常规及、十二导联体表心电图检查及测量血压,结束时对有效完整病例进行有效性及安全性评估。结果:在主要及次要观察指标方面硫酸卡维地洛及美托洛尔组均表现出较好的临床疗效,即表现在至第八周时对照组与用药组相比舒张压降低了12.96±6.55mm Hg,差异有统计学意义;试验组与用药前相比减少了12.24±5.82mm Hg,差异有统计学意义。即表现在至第八周时对照组与用药组相比收缩压降低了17.13±11.22mm Hg,差异有统计学意义;试验组与用药前相比减少了16.92±11.07mm Hg,差异有统计学意义。经统计两组组内差异有统计学意义(P0.05),但卡维地洛组与美托洛尔组组间治疗后疗效无统计学意义(P0.05)。所有入选患者,安全性检查后我们进行统计分析,未能发现两组药物对肝功能、肾功能、尿酸、血糖、血脂、白细胞及中性粒细胞有明显影响。结论:硫酸卡维地洛治疗原发性轻、中度高血压相当美托洛尔而言疗效相当,但其不良反应明显减少,治疗原发性轻、中度高血压是有效和安全的。
[Abstract]:Background: hypertension is divided into primary and secondary, of which essential hypertension accounts for 90% of the total hypertension. The direct cause of hypertension is the increase of sympathetic nervous system activity. Therefore, blocking sympathetic activity early and reducing the release of norepinephrine is one of the main mechanisms in the treatment of hypertension, which can effectively control blood pressure and reduce complications. The 尾 -receptor blocker can inhibit sympathetic nerve activity and has certain effect on the treatment of hypertension. Carvedilol is a new product of the third generation of 尾 -blockers. Its pharmacological effect is wider than that of the first and second generation of 尾 -blockers. It blocks 伪 _ 1, 尾 _ 1 and 尾 _ 2 receptors and regulates the adverse effects of catecholamine on heart, peripheral blood vessels and kidneys. Reversing the combined effects of angiotensin and receptor changes without the side effects caused by simple vasodilation or 尾 -receptor block, its antihypertensive effect and less side effects are undoubtedly an important ideal therapeutic drug for patients with hypertension. It has a good prospect of clinical application. Objective: to evaluate the efficacy and safety of carvedilol sulfate sustained-release capsule in the treatment of mild and moderate essential hypertension. The control effect of Carvedilol sulfate sustained release capsule on 24 hours blood pressure was observed by ambulatory blood pressure opening study. Methods: the patients with mild and moderate hypertension were selected strictly and then treated with Carvedilol sulfate sustained release capsule. The clinical trials were randomized, double-blind, positive drug parallel control and multicenter clinical trial. It is mainly divided into two items: one is a multicenter, randomized, double-blind, double-mimic, positive drug parallel controlled clinical study, the other is a single-arm, open, multi-center clinical study of ambulatory blood pressure. Before and after administration, blood biochemistry, blood routine, urine routine and 12-lead surface electrocardiogram were examined and blood pressure was measured. The efficacy and safety of effective and complete cases were evaluated at the end of the study. Results: carvedilol sulfate and metoprolol groups showed better clinical efficacy in the main and secondary indexes, that is, the diastolic blood pressure decreased 12.96 卤6.55mm Hg, between the control group and the medication group at the eighth week. The experimental group decreased 12.24 卤5.82mm Hg, compared with before treatment. That is to say, the systolic blood pressure decreased 17.13 卤11.22mm Hg, in the control group and 16.92 卤11.07mm Hg, in the experimental group at the eighth week. The difference between the two groups was statistically significant (P0.05), but there was no significant difference after treatment between carvedilol group and metoprolol group (P0.05). In all the patients, after safety examination, we did not find that the two groups of drugs on liver function, renal function, uric acid, blood sugar, blood lipid, white blood cells and neutrophils have a significant effect on the liver function, renal function, blood sugar, blood lipid, leukocyte and neutrophil. Conclusion: carvedilol sulfate is effective and safe in the treatment of primary mild and moderate hypertension.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R544.11

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