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: 10021704
• 负责人: Jody D. Ciolino
• 金额: $ 110.4万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 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 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021704
• 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; Stroke; Testing; Titrations; Translating; United States; Universities; Ursidae Family; Variant; Vision; base; blood pressure intervention; blood pressure reduction; blood pressure regulation; cardiovascular health; clinical practice; clinically significant; comparison group; cost effective; drug standard; efficacy evaluation; experience; hazard; health literacy; high risk; human disease; hypertension treatment; 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.

项目总结/文摘