Treatment of Hypertension In Adults with ThiaZIDES: Pragmatic Trial Pilot Study

 描述(由申请人提供)：几十年来，美国高血压治疗指南一直建议使用低剂量利尿剂，如氢氯噻嗪(HCTZ)或氯苯四氮酮(CTD)，作为分级护理方法的初始单一疗法或作为初始两种药物组合的一部分。在众多大型临床试验中，与安慰剂、常规护理或主动对照相比，基于CTD的方案显著降低了心血管事件(如中风、心力衰竭和心血管死亡率)的发生率。相比之下，很少有结果研究将基于HCTZ的治疗方案与其他治疗方法进行比较，它们通常发现HCTZ在预防心血管事件方面不如非噻嗪比较药有效。这两种药物从未在大型试验中进行过直接比较。尽管有经验证据支持CTD，但HCTZ在临床实践中的应用要广泛得多。拟议的R34是在两个大型综合卫生系统中进行的一项试点研究，以测试最终实用的随机试验的方法和可行性，比较HCTZ和CTD在预防心血管事件和死亡率方面的有效性。采用整群随机设计，我们将分配40名初级保健医生及其目前使用HCTZ的成年高血压患者(N=2,000)，将HCTZ使用者转换为CTD(干预组)或继续使用HCTZ(常规护理组)。这项试点研究和计划的全面试验将使用现有的医疗保健基础设施和电子健康记录来确定符合条件的研究对象，分发研究药物，并收集操作和结果数据。对于这项初步研究，AIM 1将记录干预措施是否按预期提供。目标2将比较干预和常规护理患者的安全性。目标3将改进试点研究设计，并使用混合方法确定干预成功的关键因素。目标4将改进样本量的估计。最后，目标5将确定确定结果的成本，并估计全面试验的每个参与者的成本。试点研究将产生必要的数据，足以为规划一项比较CTD和HCTZ的全面试验提供信息，并将推动开发实用试验的方法。

 DESCRIPTION (provided by applicant): For several decades, U.S. hypertension treatment guidelines have recommended a low-dose diuretic such as hydrochlorothiazide (HCTZ) or chlorthalidone (CTD) as initial monotherapy in a stepped-care approach or as part of an initial two-drug combination. In numerous large clinical trials, CTD-based regimens have significantly reduced rates of cardiovascular events such as stroke, heart failure, and cardiovascular mortality compared with placebo, usual care, or active comparators. In contrast, few outcome studies have compared HCTZ-based regimens with other treatments, and they have generally found HCTZ to be less effective than non-thiazide comparators in preventing cardiovascular events. The two drugs have never been compared directly in a large trial. Despite the empirical evidence favoring CTD, HCTZ is much more widely used in clinical practice. The proposed R34 is a pilot study conducted in two large integrated health systems to test methods and feasibility for an eventual pragmatic randomized trial comparing the effectiveness of HCTZ and CTD for preventing cardiovascular events and mortality. Using a cluster-randomized design, we will allocate 40 primary care physicians and their adult hypertensive patients who currently use HCTZ (N=2,000) to either convert HCTZ users to CTD (intervention group) or to continue HCTZ (usual care group). The pilot study and planned full- scale trial will use existing health care infrastructure and electronic health records to identify eligible study subjects, distribute study medication, and collect operational and outcomes data. For this pilot study, Aim 1 will document that the intervention is delivered as intended. Aim 2 will compare safety in intervention and usual care patients. Aim 3 will refine the pilot study design and identify critical factors for intervention success using a mixed-methods approach. Aim 4 will refine estimates of sample size. Finally, Aim 5 will determine the costs of ascertaining outcomes and estimate per-participant costs for the full-scale trial. The pilot study will produce data that are necessary an sufficient to inform the planning of a full-scale trial comparing CTD and HCTZ and will advance the development of methods for pragmatic trials.