CLINICAL TRIAL: AASK-ABPM

临床试验：AASK-ABPM

• 批准号: 7720969
• 负责人: Keith C Norris
• 金额: $ 1.92万
• 依托单位: CHARLES R. DREW UNIVERSITY OF MED & SCI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720969
• 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 Trials; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Creatinine clearance measurement; Data; Development; Diastolic blood pressure; Diltiazem; Doxazosin; End Point; 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; Rate; Relative (related person); Relative Risks; Renal function; Reporting; Research; 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; day; design; diabetic; falls; 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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 1。具体目的：患有高血压肾脏疾病的非裔美国人的夜间血压升高（BP）的患病率极高。降低夜间BP是否可以防止该人群中的心血管 - 肾脏并发症，这是降低夜间BP的可行性。这项试点研究是一项长期研究计划的第一步，该计划将确定夜间血压降低作为治疗性干预在高血压慢性肾脏疾病中的作用。在这项试验研究中，将使用确定为有效和安全的策略将在较大的试验中使用，以评估其对临床终点的影响。这项试验研究的总体目标是确定两种基于雷米普利的Ntihypertengengengeny策略的影响，每个策略旨在降低夜间bp bp a特定目标1确定相对于常规治疗的每种策略对夜间bp的影响。具体目标2确定相对于常规治疗的每种策略对诊所BP，白天BP，24小时BP和浸入状态的影响。 2。在几项观察性研究中，背景和理由升高的夜间BP与不良肾脏和心血管结局有关。例如，在Piuma的研究中，非汗水的女性比dipper（相对风险，6.79，P0.05）的心血管发病率高六倍。1在Syst-EUR研究中，Systolot BP的夜间/日率每天每天增加10％，心血管事件的风险，心血管事件的风险增加了41％（p = 0.03）。 Sturrock等人表明，北极光的死亡率低于非浸水者（8 vs 26％，p = 0.04），并且出现肾功能不全的非浸水者的死亡率最高（42％）。3与常规的BP测量相比，ABPM与微αBumbuminuria的存在和/或幅度密切相关。 4,5-7此外，BP夜间下降钝化的患者更有可能患有微量白蛋白尿。一些小型研究前瞻性地评估了ABPM与肾功能下降与蛋白尿之间的关系。 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夜间舒张期跌落（r = 0.61，p 0.001）.9在最近的一项前瞻性研究中，该研究招募了75名患有正常尿白蛋白排泄和血压正常的1型糖尿病的年轻人，睡眠期间的收缩压升高为微量脂肪症的发展。在睡眠期间的血压正常降低的人中，从正常白蛋白排泄到微量白蛋白尿的可能性较小。10如随后所述，来自AASK队列研究的横截面数据得到了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BP是否会降低肾脏和心血管疾病的风险？据我们所知，没有任何试验解决这个问题，也许是因为有关干预措施可能会降低夜间BPS的信息很少。两项试验，一个在欧洲，一项在日本解决了这一可行性问题。在148名非猛攻高血压患者中，Hermida等人表明，瓦尔萨坦的PM给药导致75％的患者的转化为北斗七星的概况，而与AM给药相比，AM的13/8.5 mmHg相比，AM vs.14.7/10.3 mmHg的PM中的13/8.5 mmHg相比，平均BP的平均降低平均降低。 24小时平均BP的减少相似（AM为7.2 mmHg，PM为5.2 mmHg），但与AM给药的PM给药的平均夜间时间BP更高（11 mmHg）与AM给药相比（3.6 mMHG）（3.6 mMHG）。12其他研究使用了13-15 doxazosin，13-15 nisoldipine，diserdipine，dirister，deriSter，derapamiral derapamiral nipapamil nipapamil nipApamIl。 161718，这些研究不包括非洲裔美国人，慢性肾脏疾病患者或多种药物方案的个体，即心血管 - 肾脏结局的高风险患者，这些患者在临床结果试验中将在逻辑上成为研究人群。正在进行的临床试验研究正在进行中，日本晨振-1（JMS-1）正在评估使用α受体阻滞剂通过alpha-blocker，夜间多克萨斯素在夜间以及在需要时加上β受体阻滞剂（如果需要）的严格早晨血压控制是否可以减少高血压目标器官。19 在预防评估（HOPE）研究中，雷米普里是在夜间作为协议的一部分进行管理的。这项研究表明，与安慰剂相比，拉米普利组的心血管风险显着降低。20夜间血压减少是否导致心血管风险降低，无法证实，但这是一个合理的考虑因素。