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推荐低剂量利尿剂，如氢氯噻嗪（HCTZ）或氯噻酮（CTD）作为阶梯式护理方法中的初始单药治疗或作为初始两药联合治疗的一部分。在许多大型临床试验中，与安慰剂、常规护理或活性对照药物相比，基于CTD的方案显著降低了心血管事件（如卒中、心力衰竭和心血管死亡率）的发生率。相比之下，很少有结局研究将HCTZ为基础的方案与其他治疗进行比较，并且他们通常发现HCTZ在预防心血管事件方面不如非噻嗪类对照药物有效。这两种药物从未在大型试验中进行过直接比较。尽管经验证据支持CTD，但HCTZ在临床实践中的应用更为广泛。拟议的R34是一项在两个大型综合卫生系统中进行的试点研究，旨在测试方法和可行性，以便最终进行一项实用的随机试验，比较HCTZ和CTD预防心血管事件和死亡率的有效性。采用分组随机设计，我们将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）分配为将HCTZ使用者转换为CTD（干预组）或继续HCTZ（常规护理组）。试点研究和计划中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合格的研究受试者，分发研究药物，并收集操作和结果数据。对于这项试点研究，目标1将记录干预措施是否按预期实施。目标2将比较干预和常规护理患者的安全性。目标3将完善试点研究设计，并使用混合方法确定干预成功的关键因素。目标4将完善样本量的估计。最后，目标5将确定确定结果的成本，并估计全面试验的每位参与者成本。试点研究将产生必要的数据，足以为比较CTD和HCTZ的全面试验的规划提供信息，并将推动实用试验方法的发展。

 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.