A double-blind randomized controlled trial to assess the efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA)

项目摘要/摘要 拟议的申请将调查是否开始使用超低剂量四联疗法- 联合治疗(包括厄贝沙坦37.5mg.氨氯地平1.25mg.吲达帕胺0.625 mg. 比索洛尔2.5毫克)将降低12小时的自动化办公室血压和24小时动态血压 与开始标准剂量的单一疗法相比，几周更有效，副作用不增加 (厄贝沙坦150毫克)用于血压升高的成年人(SBP&GT；140 mm Hg或DBP&Gt；90 mm Hg)和没有血压升高的成年人 心血管疾病。我们对18名参与者进行的短期(4周)交叉试验的初步数据 提示LDQT与未服用安慰剂相比，办公室血压平均降低22/13毫米汞柱 严重不良事件的差异。对24小时动态血压的影响也相似。 我们将在联邦资格认证的网络中进行这项第二阶段的单站点随机对照试验 芝加哥的健康中心，因为这一人群背负着不成比例的血压负担 我们之前已经成功地在这一人群中进行了临床研究。这一新的和 更简单的治疗模式有可能消除这一人群中的血压差异，这 为这项提议提供了动力。虽然我们假设这一干预将很容易实施， 对所有患者和临床医生都有效，我们将通过潜在的调节来探索治疗效果的变化 变量，包括年龄、性别、种族/民族和健康素养水平。除了检查疗效，我们还计划 通过同时评估在临床环境中实施该干预措施的可行性 LDQT在患者和临床医生中的可接受性、偏好和经验教训的实施结果。 两名早期研究人员将领导研究团队，拥有相关的、互补的临床试验经验 在心血管医学和生物统计学方面，这为这一提议提供了坚实的基础。我们的团队会 利用内部和外部在心血管研究、联合药物治疗、 和实施科学研究一种新的干预高负担、低资源人群的方法 通过此第二阶段试验的单一站点。我们计划将目前的试验数据与在2009年进行的类似试验的数据进行合并 澳大利亚(由本建议中的一名研究小组成员领导)检查稳健性和 我们的研究结果的概括性。 相关性 本提案旨在创建、评估和演示成功实施超低剂量 四联用药疗法比标准疗法更简单、更有效、更安全 病人和他们的医生。如果成功，该提案将为更大的多站点第三阶段奠定基础 随机对照试验，目的是在更大的人群中证实有效性和安全性，最终 目标是彻底改变最初的降压治疗模式。

PROJECT SUMMARY/ABSTRACT The proposed application will investigate whether initiating treatment with ultra-low-dose quadruple- combination therapy (LDQT; including irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) will lower automated office blood pressure and 24-hour ambulatory blood pressure at 12 weeks more effectively, and with no increase in side effects, compared to initiating standard dose monotherapy (irbesartan 150 mg) in adults with raised blood pressure (SBP>140 mmHg or DBP>90 mmHg) and without cardiovascular disease. Our preliminary data from a short-term (4-week) crossover trial of 18 participants suggest that LDQT lowers office blood pressure by 22/13 mmHg on average compared with placebo with no difference in serious adverse events. Effects on 24-hour ambulatory blood pressure were similar. We will perform this phase II, single site, randomized controlled trial in a network of federally qualified health centers in Chicago because this population bears a disproportionate burden of blood pressure related diseases, and we have previously successfully conducted clinical studies in this population. This new and simpler treatment paradigm has potential to eliminate blood pressure disparities in this population, which provides the motivation for this proposal. While we hypothesize this intervention will be easily implemented and efficacious for all patients and clinicians, we will explore variation in treatment effect by potential moderating variables, including age, sex, race/ethnicity, and health literacy level. Beyond examining efficacy, we also plan to assess feasibility of implementing this intervention in a clinical setting by simultaneously evaluating implementation outcomes of acceptability, preferences, and lessons of LDQT among patients and clinicians. Two early stage investigators will lead the study team with relevant, complementary clinical trial experience in cardiovascular medicine and biostatistics, which provide a strong foundation for this proposal. Our team will leverage internal and external experience and resources in cardiovascular research, combination drug therapy, and implementation science to study a novel intervention in a high-burden, low-resource population from a single site through this phase II trial. We plan to pool the present trial data with that of similar trial conducted in Australia (led by one of the study team members in this proposal) to examine the robustness and generalizability of our study results. Relevance This proposal aims to create, evaluate, and demonstrate successful implementation of an ultra-low dose quadruple combination drug therapy that is simpler, more efficacious, and safer than standard therapy for patients and their doctors. If successful, then the proposal will lay the framework for a larger multi-site phase III randomized controlled trial with goal of confirming efficacy and safety in a larger population, with the ultimate goal of a complete change the paradigm for initial blood pressure lowering therapy.