中国脑卒中一级预防试验 (CSPPT)
马来酸依那普利和叶酸片剂用于高血压患者卒中的一级预防:一项上市后、双盲、随机对照试验。
研究概览
详细说明
原发性高血压是导致心血管事件最重要的危险因素。 成功控制高血压是预防这些事件的关键。 高同型半胱氨酸血症 (HHcy) 是另一个独立的危险因素,尤其是中风。 我们团队对中国 39165 名受试者进行的前瞻性巢式病例对照研究表明,心血管事件(尤其是中风)的发生率与血浆总同型半胱氨酸 (tHcy) 水平密切相关。 与没有这两种危险因素的受试者相比,高血压和 HHcy 的共存使中风的风险显着增加 25 至 30 倍(Graham 等人,1997)。 以往和我们的研究结果清楚地表明,同时控制高血压和 HHcy 是降低中国心血管事件发病率和死亡率的关键。
已充分证明叶酸可有效降低血浆 tHcy 水平。 虽然关于其预防心血管事件的功效仍有争议,但我们团队所做的一项研究:“补充叶酸在中风预防中的功效:一项荟萃分析”(Wang 等人,2007 年)提供了一致的证据表明补充叶酸可以降低中风的风险增加 18%,而在没有强化叶酸或用于一级预防的人群中,中风的风险增加 25%。
5,10-亚甲基四氢叶酸还原酶(MTHFR)的C677T基因多态性是血浆tHcy水平的遗传决定因素之一。 观察性研究表明,具有 TT 基因型的个体往往具有较高的血浆 tHcy 和较高的心血管事件风险(Cronin 等人,2005 年),补充叶酸可显着降低血浆 tHcy。 简而言之,其他人和我们团队之前的研究为我们提议的试验提供了强有力的理由,详述如下。
目前研究的假设是,抗高血压药物(如依那普利)与叶酸的组合不仅有效,而且比单独使用抗高血压药物(如依那普利)预防高血压患者中风更安全且具有更高的成本效益.
该试验将招募 20,000 名具有已知 MTHFR C677T 基因型的原发性高血压患者。 受试者将首先按基因型分层,然后随机分配到治疗组。 将指导研究患者每天口服依那普利 10 毫克或依那普利/叶酸 10 毫克/0.8 毫克 每日片剂最多 5 年。 每 3 个月进行一次随访。
首次卒中发作(主要终点)或复合心血管事件的发生率和时间用作终点。 它们将按治疗组进行比较,有和没有按 C677T 基因多态性分层。 还将测试治疗组和 C677T 基因多态性对疗效的潜在相互作用。
这将是在中国人群中进行的此类试验中的首次也是规模最大的试验。 该试验的结果可能有可能将当前的临床和公共卫生发现转化为实践。
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
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Anhui
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Anqing City、Anhui、中国、246000
- Anqing Branch, Anhui Institute of Biomedical Research
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Jiangsu
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Lianyungang、Jiangsu、中国、222003
- Lianyungang Center for Advanced Research in Cardiovascular Diseases
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
纳入标准:
- 两次筛查访视的血压均≥140/90 mmHg 或目前正在接受抗高血压治疗
- 45 - 75 岁
- 成功测定MTHFR C677T基因型
- 对于绝经前妇女,同意在试验期间使用避孕药具
- 签署书面知情同意书
排除标准:
- 有中风病史
- 有心肌梗塞病史
- 有医生诊断为心力衰竭的病史
- 冠状动脉血运重建后
- 癌症等严重躯体疾病
- 继发性高血压
- 先天性或获得性器质性心脏病
- 血管紧张素转换酶抑制剂(ACEI)禁忌
- ACEI不良反应史
- 目前长期服用叶酸或维生素B12或维生素B6
- 孕妇或哺乳期妇女
- 严重精神障碍
- 表明肝或肾功能异常的实验室检查
- 不愿参加试验,不愿改变目前的降压治疗
学习计划
研究是如何设计的?
设计细节
- 主要用途:预防
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:依那普利/叶酸
给予固定组合药物。
剂量固定为每天依那普利 10 毫克/叶酸 0.8 毫克。
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依那普利/叶酸,(10mg依那普利/0.8mg
叶酸)/片剂,口服,每日一次,最长服用 5 年。
允许与其他抗高血压药物联合使用。
其他名称:
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有源比较器:依那普利
每天给予马来酸依那普利 10 毫克
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依那普利,10mg/片,每天口服一次,最多连续服用 5 年。
允许与其他抗高血压药物联合使用。
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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症状性中风的首次发作(缺血性或出血性)
大体时间:试用期间
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每 3 个月对患者进行一次随访。
所有终点结果均由研究的终点裁决委员会评估。
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试用期间
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次要结果测量
结果测量 |
大体时间 |
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复合主要心血管事件
大体时间:试用期间
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试用期间
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全因死亡
大体时间:试用期间
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试用期间
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首次发作缺血性中风并导致死亡
大体时间:试用期间
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试用期间
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首次发作出血性中风并因此死亡
大体时间:试用期间
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试用期间
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心肌梗塞和由此导致的死亡
大体时间:试用期间
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试用期间
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其他结果措施
结果测量 |
大体时间 |
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恶性肿瘤
大体时间:试用期间
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试用期间
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合作者和调查者
调查人员
- 首席研究员:Yong Huo, M.D.、The First Hospital, Beijing University
出版物和有用的链接
一般刊物
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- Yang X, Zhang M, Song R, Liu C, Huo Y, Qian G. The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT. Cardiovasc Ther. 2018 Dec;36(6):e12473. doi: 10.1111/1755-5922.12473. Epub 2018 Nov 20.
- Nie J, Xie L, Zhao BX, Li Y, Qiu B, Zhu F, Li GF, He M, Wang Y, Wang B, Liu S, Zhang H, Guo H, Cai Y, Huo Y, Hou FF, Xu X, Qin X. Serum Trimethylamine N-Oxide Concentration Is Positively Associated With First Stroke in Hypertensive Patients. Stroke. 2018 Sep;49(9):2021-2028. doi: 10.1161/STROKEAHA.118.021997. Erratum In: Stroke. 2019 Jun;50(6):e175.
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研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
依那普利/叶酸的临床试验
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Gladwin, Mark, MDNational Heart, Lung, and Blood Institute (NHLBI); Complexa, Inc.终止
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University College, LondonImperial College London; Cancer Research UK; National Cancer Imaging Translational Accelerator招聘中
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University of Colorado, DenverNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)招聘中