血管紧张素受体脑啡肽酶抑制剂与血管紧张素受体阻滞剂在老年人群中测量动脉僵硬度的前瞻性比较（PARAMETER）研究的原理与研究设计
Rationale and study design of the Prospective comparison of Angiotensin Receptor neprilysin inhibitor with Angiotensin receptor blocker MEasuring arterial sTiffness in the eldERly (PARAMETER) study.
作者信息
Williams Bryan, Cockcroft John R, Kario Kazuomi, Zappe Dion H, Cardenas Pamela, Hester Allen, Brunel Patrick, Zhang Jack
机构信息
Department of Cardiovascular Sciences and National Institute for Health Research (NIHR) University College London (UCL) Hospitals Biomedical Research Centre, University College London, London, UK.
出版信息
BMJ Open. 2014 Feb 4;4(2):e004254. doi: 10.1136/bmjopen-2013-004254.
INTRODUCTION
Hypertension in elderly people is characterised by elevated systolic blood pressure (SBP) and increased pulse pressure (PP), which indicate large artery ageing and stiffness. LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is being developed to treat hypertension and heart failure. The Prospective comparison of Angiotensin Receptor neprilysin inhibitor with Angiotensin receptor blocker MEasuring arterial sTiffness in the eldERly (PARAMETER) study will assess the efficacy of LCZ696 versus olmesartan on aortic stiffness and central aortic haemodynamics.
METHODS AND ANALYSIS
In this 52-week multicentre study, patients with hypertension aged ≥60 years with a mean sitting (ms) SBP ≥150 to <180 and a PP>60 mm Hg will be randomised to once daily LCZ696 200 mg or olmesartan 20 mg for 4 weeks, followed by a forced-titration to double the initial doses for the next 8 weeks. At 12-24 weeks, if the BP target has not been attained (msSBP <140 and ms diastolic BP <90 mm Hg), amlodipine (2.5-5 mg) and subsequently hydrochlorothiazide (6.25-25 mg) can be added. The primary and secondary endpoints are changes from baseline in central aortic systolic pressure (CASP) and central aortic PP (CAPP) at week 12, respectively. Other secondary endpoints are the changes in CASP and CAPP at week 52. A sample size of 432 randomised patients is estimated to ensure a power of 90% to assess the superiority of LCZ696 over olmesartan at week 12 in the change from baseline of mean CASP, assuming an SD of 19 mm Hg, the difference of 6.5 mm Hg and a 15% dropout rate. The primary variable will be analysed using a two-way analysis of covariance.
ETHICS AND DISSEMINATION
The study was initiated in December 2012 and final results are expected in 2015. The results of this study will impact the design of future phase III studies assessing cardiovascular protection.
CLINICAL TRIALS IDENTIFIER
EUDract number 2012-002899-14 and ClinicalTrials.gov NCT01692301.
引言
老年人高血压的特点是收缩压（SBP）升高和脉压（PP）增加，这表明大动脉老化和僵硬。LCZ696是首个血管紧张素受体脑啡肽酶抑制剂（ARNI），正被开发用于治疗高血压和心力衰竭。老年患者中血管紧张素受体脑啡肽酶抑制剂与血管紧张素受体阻滞剂测量动脉僵硬度的前瞻性比较（PARAMETER）研究将评估LCZ696与奥美沙坦对主动脉僵硬度和中心主动脉血流动力学的疗效。
方法与分析
在这项为期52周的多中心研究中，年龄≥60岁、平均坐位（ms）SBP≥150至<180且PP>60 mmHg的高血压患者将被随机分为每日一次LCZ696 200 mg或奥美沙坦20 mg，治疗4周，随后在接下来的8周内强制滴定至初始剂量的两倍。在12 - 24周时，如果未达到血压目标（msSBP<140且ms舒张压<90 mmHg），可添加氨氯地平（2.5 - 5 mg），随后添加氢氯噻嗪（6.25 - 25 mg）。主要终点和次要终点分别是第12周时中心主动脉收缩压（CASP）和中心主动脉PP（CAPP）相对于基线的变化。其他次要终点是第52周时CASP和CAPP的变化。估计随机入组432例患者的样本量可确保90%的检验效能，以评估第12周时LCZ696相对于奥美沙坦在平均CASP基线变化方面的优越性，假设标准差为19 mmHg，差异为6.5 mmHg，脱落率为15%。主要变量将采用双向协方差分析。
伦理与传播
该研究于2012年12月启动，预计2015年得出最终结果。本研究结果将影响未来评估心血管保护作用的III期研究设计。
临床试验标识符
欧盟临床试验编号2012 - 002899 - 14以及美国国立医学图书馆临床试验注册中心编号NCT01692301。
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