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

评估四联超低剂量治疗高血压的有效性和安全性的双盲随机对照试验（QUARTET USA）

• 批准号: 10596921
• 负责人: Jody D. Ciolino
• 金额: $ 62.9万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10596921
• 关键词: Adherence; Adult; Age; American; Amlodipine; Australia; Biometry; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chicago; Chronic; Clinic Visits; Clinical; Clinical Practice Guideline; Clinical Research; Clinical Trials; Combination Drug Therapy; Combined Modality Therapy; Community Health Networks; Conduct Clinical Trials; Cross-Over Trials; Data; Development; Disease; Dose; Double-Blind Method; Essential Hypertension; Ethnic Origin; Event; Federally Qualified Health Center; Foundations; Goals; Heart Diseases; Hematological Disease; Heterogeneity; Hour; Hybrids; Hydrochlorothiazide; Hypertension; Individual; Intervention; Intervention Trial; Lead; Lung diseases; Medicine; Methods; Mission; Motivation; Myocardial Infarction; National Heart, Lung, and Blood Institute; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Population; Prevention trial; Race; Randomized Controlled Trials; Research; Research Personnel; Resources; Risk; Safety; Serious Adverse Event; Site; Sleep Disorders; Strategic vision; Stroke; Testing; Titrations; Translating; United States; Universities; Ursidae Family; Variant; base; blood pressure control; blood pressure intervention; blood pressure reduction; cardiovascular health; clinical practice; clinically significant; comparison group; cost effective; drug standard; efficacy evaluation; experience; hazard; health literacy; high risk; human disease; hypertension treatment; hypertensive; implementation evaluation; implementation outcomes; implementation science; improved; irbesartan; medical schools; member; novel; novel therapeutic intervention; phase II trial; pill; population based; preference; prevent; sex; side effect; success; treatment effect

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.

项目摘要/摘要 拟议的申请将调查是否使用超低剂量四倍体进行治疗 - 联合疗法（LDQT；包括Irbesartan 37.5 mg，氨氯地平1.25 mg，indapamide 0.625 mg和 Bisoprol 2.5 mg）将降低自动化办公室血压和24小时的动态血压12 与启动标准剂量单一疗法相比，更有效的几周，副作用没有增加 （IRBESARTAN 150 mg）在血压升高（SBP> 140 mmHg或DBP> 90 mmHg）的成年人中，没有 心血管疾病。我们来自18名参与者的短期（4周）跨界试验的初步数据 建议LDQT平均将办公室血压降低22/13 mmHg，而安慰剂则无 严重不良事件的差异。对24小时门诊血压的影响相似。 我们将在联邦资格的网络中执行II阶段，单个站点，随机对照试验 芝加哥的卫生中心是因为这个人口承担与血压相关的不成比例的负担 疾病，我们以前已经成功地在该人群中进行了临床研究。这个新的和 更简单的治疗范式有可能消除该人群中的血压差异，这 提供了该建议的动力。尽管我们假设这种干预将很容易实施，并且 对于所有患者和临床医生，我们将通过潜在的调节来探索治疗效果的差异 变量，包括年龄，性别，种族/种族和健康素养水平。除了检查功效外，我们还计划 通过同时评估，评估在临床环境中实施此干预措施的可行性 患者和临床医生中LDQT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具有相关的互补临床试验经验 在心血管医学和生物统计学方面，为该建议提供了巨大的基础。我们的团队会 利用心血管研究，联合药物治疗的内部和外部经验和资源， 和实施科学，以研究来自高负荷，低农产品的新干预措施 通过此II阶段试验的单个站点。我们计划使用在 澳大利亚（由本提案中的一名研究团队成员领导），以检查鲁棒性和 我们研究结果的普遍性。 关联 该建议旨在创建，评估和展示超低剂量的成功实施 与标准疗法更简单，更有效，更安全 病人及其医生。如果成功，则该提案将为较大的多站点III奠定框架 随机对照试验的目标是确认较大人群的功效和安全性，并具有最终 完全改变初始血压降压疗法的范式的目标。