CLINICAL TRIAL: AASK-ABPM

临床试验：AASK-ABPM

• 批准号: 7960760
• 负责人: Keith C Norris
• 金额: $ 0.16万
• 依托单位: CHARLES R. DREW UNIVERSITY OF MED & SCI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2009-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960760
• 关键词: Address; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; African American; Albumins; Beds; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Chronic Kidney Failure; Clinic; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Creatinine clearance measurement; Data; Development; Diastolic blood pressure; Diltiazem; Doxazosin; Enrollment; Europe; Evaluation Studies; Event; Excretory function; Funding; Goals; Grant; Heart; High Prevalence; Hour; Individual; Institution; Insulin-Dependent Diabetes Mellitus; Intervention; Japan; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Measurement; Microalbuminuria; Morbidity - disease rate; Nisoldipine; Observational Study; Organ; Outcome; Patients; Pharmaceutical Preparations; Pilot Projects; Placebos; Population; Population Study; Prospective Studies; Proteinuria; Protocols documentation; Ramipril; Relative (related person); Relative Risks; Renal function; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Risk; Role; Sleep; Source; Sympathetic Nervous System; Therapeutic Intervention; Time; Treatment Protocols; United States National Institutes of Health; Woman; base; blood pressure regulation; cardiovascular risk factor; design; diabetic; falls; high risk; mortality; prevent; prevention evaluation; trandolapril; urinary; valsartan; young adult

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1. Specific Aims: African-Americans with hypertensive kidney disease have an extremely high prevalence of elevated nocturnal blood pressure (BP). Whether reducing nocturnal BP prevents cardiovascular-renal complications in this population is unknown, as is the feasibility of lowering nocturnal BP. This pilot study is the first step in a long-term research initiative that will determine the role of nocturnal blood pressure reduction as a therapeutic intervention in hypertensive chronic kidney disease. Strategies identified as effective and safe in this pilot study will be used in larger trials to evaluate their effect on clinical end points. The overall goal of this pilot study is to determine the effects of two ramipril based ntihypertensive regimen strategies, each designed to lower nocturnal BP a Specific Aim 1 Determine the effects of each strategy, relative to usual treatment, on nocturnal BP. Specific Aim 2 Determine the effects of each strategy, relative to usual treatment, on clinic BP, daytime BP, 24 hour BP, and dipping status. 2. Background and rationale Elevated nocturnal BP has been associated with adverse renal and cardiovascular outcomes in several observational studies. For example, in the PIUMA study, women who were non-dippers had six fold higher cardiovascular morbidity than dippers (relative risk, 6.79, p0.05).1 In the Syst-Eur study, for every 10% higher night/day ratio of systolic BP, the risk of cardiovascular events was increased by 41% (p=0.03).2 In a small, but provocative retrospective analysis of diabetics, Sturrock et al demonstrated that dippers had a lower mortality than non-dippers (8 vs 26%, p=0.04) and that non-dippers who developed renal insufficiency had the highest mortality (42%).3 Compared to conventional BP measurements, ABPM is more closely associated with the presence and/or magnitude of microalbuminuria. 4,5-7 In addition, patients with a blunted nocturnal decline in BP are more likely to have microalbuminuria. A few small studies have prospectively evaluated the relationship between ABPM and decline in renal function and proteinuria. In a 3 year prospective study, Timio etal demonstrated that the non-dippers had a faster rate of creatinine clearance decline than the dippers (0.37¿ 0.2 vs. 0.27¿ 0.09 ml/min/month; p = 0.002).8 In another study, a significant association was reported between the decline in creatinine clearance over a 24-month period and average nighttime diastolic BP (r = 0.52, p = 0.001) and nocturnal diastolic fall (r = 0.61, p 0.001).9 In a recent prospective study that enrolled 75 young adults with type 1 diabetes with normal urinary albumin excretion and blood pressure, an increase in systolic blood pressure during sleep preceded the development of microalbuminuria. In those whose blood pressure during sleep decreased normally, the progression from normal albumin excretion to microalbuminuria was less likely.10 As described subsequently, cross-sectional data from the AASK cohort study corroborates and extends these observations. The results of these observational studies raise a critical research question, namely, does lowering nocturnal BP reduce the risk of renal and cardiovascular disease? To our knowledge, no trial has addressed this issue, perhaps because there is scant information about interventions that might lower nocturnal BPs. Two trials, one in Europe and one in Japan, have addressed this feasibility issue. In 148 non-dipper hypertensive patients, Hermida et al demonstrated that PM administration of valsartan resulted in the conversion to a dipper profile in 75% of patients while achieving similar 24 hour mean BP reduction compared to AM administration (13/8.5 mmHg in AM vs 14.7/10.3 mmHg in PM).11 Similarly, Kuroda et al compared AM versus PM administration of trandalopril in 37 patients. Reduction in 24 hour mean BP was similar (7.2 mmHg in AM, 5.2 mmHg in PM), but reduction of mean night time BP was higher with the PM administration of trandolapril (11 mm Hg) compared to the AM administration (3.6 mm Hg).12 Other studies have used doxazosin,13-15 nisoldipine, diltiazem or verapamiladministered at bed time. 161718However, these studies did not include African-Americans, patients with chronic kidney disease, or individuals on multiple drug regimens, that is, patients at high risk for cardiovascular-renal outcomes who would be logically the study population in a clinical outcome trial. An ongoing clinical trial study in progress, the Japan Morning Surge-1 (JMS-1), is evaluating whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin at night time and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.19 In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril was administered at night time as a part of the protocol. This study showed significant reduction in cardiovascular risk in the ramipril group compared to placebo.20 Whether night time blood pressure reduction contributed to reduction in cardiovascular risk cannot be confirmed, but is a reasonable consideration.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 1.特定目的：患有高血压肾病的非洲裔美国人夜间血压（BP）升高的患病率极高。 降低夜间血压是否能预防这一人群的心血管-肾脏并发症尚不清楚，降低夜间血压的可行性也是未知的。这项初步研究是长期研究计划的第一步，该计划将确定夜间血压降低作为高血压慢性肾脏病治疗干预的作用。在这项初步研究中确定为有效和安全的策略将用于更大规模的试验，以评估其对临床终点的影响。 这项初步研究的总体目标是确定两种基于雷米普利的降压方案策略的效果，每种策略都旨在降低夜间血压。具体目标1确定每种策略相对于常规治疗对夜间血压的影响。 具体目标2确定每种策略相对于常规治疗对门诊血压、日间血压、24小时血压和下降状态的影响。 2.背景和原理在几项观察性研究中，夜间血压升高与不良肾脏和心血管结局相关。例如，在PIUMA研究中，非勺型女性的心血管发病率是勺型女性的六倍（相对风险，6.79，p0.05）。1在Syst-Eur研究中，收缩压夜/日比值每增加10%，心血管事件风险增加41%（p=0.03）。2在一项小规模但具有争议性的糖尿病回顾性分析中，Sturrock等人证明，杓型糖尿病患者的死亡率低于非杓型糖尿病患者。（8 vs 26%，p=0.04），非勺型肾功能不全患者的死亡率最高（42%）。3 与传统的血压测量相比，ABPM与微量白蛋白尿的存在和/或程度更密切相关。4，5 -7此外，夜间血压下降不明显的患者更有可能出现微量白蛋白尿。一些小型研究前瞻性地评估了ABPM与肾功能下降和蛋白尿之间的关系。在一项为期3年的前瞻性研究中，Timio埃塔尔证明，非勺型患者的肌酐清除率下降速度比勺型患者快（0.37 <$0.2 vs 0.27 <$0.09 ml/min/月; p = 0.002）。8在另一项研究中，据报道，24个月内肌酐清除率下降与平均夜间舒张压之间存在显著相关性（r = 0.52，p = 0.001）和夜间舒张压下降（r = 0.61，p 0.001）。9在最近的一项前瞻性研究中，招募了75名尿白蛋白排泄和血压正常的1型糖尿病年轻成人，睡眠期间收缩压升高先于微量白蛋白尿的发生。 在睡眠期间血压正常下降的患者中，从正常白蛋白排泄进展为微量白蛋白尿的可能性较小。10如随后所述，来自AASK队列研究的横断面数据证实并扩展了这些观察结果。 这些观察性研究的结果提出了一个关键的研究问题，即降低夜间血压是否会降低肾脏和心血管疾病的风险？ 据我们所知，没有试验解决了这个问题，也许是因为缺乏关于可能降低夜间血压的干预措施的信息。 两项试验，一项在欧洲，一项在日本，已经解决了这个可行性问题。在148例非杓型高血压患者中，Hermida et al证实，缬沙坦PM给药导致75%的患者转为杓型，同时与AM给药相比，24小时平均血压降低相似（上午13/8.5 mmHg vs下午14.7/10.3 mmHg）。11类似地，黑田等人在37例患者中比较了上午与下午的群达普利给药。 24小时平均血压的降低相似（上午7.2 mmHg，下午5.2 mmHg），但与上午给药（3.6 mmHg）相比，群多普利下午给药（11 mmHg）的平均夜间血压降低更高。12其他研究使用了多沙唑嗪、尼索地平、地尔硫卓或维拉帕米在睡前给药。161718然而，这些研究不包括非裔美国人、慢性肾脏疾病患者或接受多种药物治疗方案的个体，即心血管-肾脏结局高风险患者，这些患者在逻辑上是临床结局试验的研究人群。 一项正在进行的临床试验研究，日本早晨浪涌-1（JMS-1），正在评估通过在夜间使用α-受体阻滞剂多沙唑嗪并在必要时添加β-受体阻滞剂进行交感神经系统阻滞来严格控制早晨血压是否可以减少高血压靶器官损害。 在心脏结局预防评价（HOPE）研究中，作为方案的一部分，在夜间给予雷米普利。这项研究表明，与安慰剂相比，雷米普利组的心血管风险显著降低。20夜间血压降低是否有助于心血管风险降低尚不能证实，但这是一个合理的考虑因素。