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

项目总结/摘要 拟议的申请将调查是否开始治疗超低剂量的四倍- 联合治疗（LDQT;包括厄贝沙坦37.5 mg，舒巴坦1.25 mg，吲达帕胺0.625 mg，和 比索洛尔2.5 mg）将降低自动办公室血压和12小时24小时动态血压 与开始标准剂量单药治疗相比， （厄贝沙坦150 mg）在血压升高（SBP>140 mmHg或DBP>90 mmHg）和无 心血管疾病我们的初步数据来自18名参与者的短期（4周）交叉试验 表明LDQT与安慰剂相比平均降低办公室血压22/13 mmHg， 严重不良事件的差异。对24小时动态血压的影响相似。 我们将在一个有联邦资格的网络中进行这项II期、单中心、随机对照试验。 芝加哥的健康中心，因为这一人群承担着不成比例的血压相关负担 疾病，我们以前已经成功地在这一人群中进行了临床研究。这个新的和 更简单的治疗模式有可能消除这一人群的血压差异， 提供了这个提议的动机。虽然我们假设这种干预很容易实施， 对所有患者和临床医生有效，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的可行性， 实施结果的可接受性，偏好，并在患者和临床医生LDQT的教训。 两名早期研究者将领导研究团队，并具有相关、互补的临床试验经验 在心血管医学和生物统计学，这为这一建议提供了坚实的基础。我们的团队将 利用心血管研究、联合药物治疗、 和实施科学，研究一种新的干预措施，在一个高负担，低资源的人口从一个 通过这个II期试验。我们计划把现时的试验数据与一九九九年进行的同类试验数据合并， 澳大利亚（由本提案中的一名研究小组成员领导），以审查 我们的研究结果的普遍性。 相关性 该提案旨在创建、评估和演示超低剂量 四联联合药物治疗比标准治疗更简单，更有效，更安全， 病人和他们的医生。如果成功的话，那么该提案将为更大的多站点第三阶段奠定框架 随机对照试验，目的是在更大人群中确认疗效和安全性，最终 目标是彻底改变初始降压治疗的模式。

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.