A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients with Acute Heart Failure

方案利尿疗法与标准护理在急诊室急性心力衰竭患者中的​​随机试验

• 批准号: 10507806
• 负责人: SEAN PATRICK COLLINS
• 金额: $ 85.93万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10507806
• 关键词: Accident and Emergency department; Acute; Admission activity; Adverse event; Amiloride; Blinded; Body Weight decreased; Cardiovascular system; Caring; Cessation of life; Clinical; Clinical Trials; Congestive; Consensus; Consumption; Data; Death Rate; Development; Diuretics; Dose; Dyspnea; Effectiveness; Emergency Department evaluation; Emergency Department patient; Enrollment; Ensure; Excretory function; Future; Guidelines; Heart failure; Hospitalization; Hospitals; Hour; Inpatients; Insulin; Intervention; Intravenous; Investigation; Length of Stay; Level of Evidence; Liquid substance; Measurement; Measures; Mediating; Nurses; Outcome; Outpatients; Pathway interactions; Patient Care; Patients; Personal Satisfaction; Precision therapeutics; Protocols documentation; Randomized; Residual state; Resistance; Resolution; Resources; Risk; Role; Route; Slide; Sodium; Spottings; Standardization; Structure; Testing; Therapeutic Trials; Time; Titrations; Treatment Failure; Treatment Protocols; Urine; Visual; Work; analog; base; clinical care; design; epithelial Na+ channel; experience; hospital readmission; improved; improved outcome; individual response; inhibitor; mortality; novel; personalized strategies; prevent; primary outcome; pro-brain natriuretic peptide (1-76); randomized trial; readmission rates; reduce symptoms; response; secondary outcome; standard care; success; symptomatic improvement; treatment arm; treatment as usual; treatment strategy; trial comparing; urinary; usual care arm

Abstract Of the one million emergency department (ED) patients hospitalized with acute heart failure (AHF), loop diuretics are the only IV treatment used over 80% of the time, although only with level of evidence C. Prior studies have focused on the initial dose of IV diuretic and failed to find one strategy with maximal efficacy. Diuretic dosing and response vary widely, leaving many patients inadequately treated. Some have a clinical response to diuretic therapy resulting in symptom improvement and discharge from the hospital within 3-5 days. However, despite apparent symptom improvement, 50% of these patients experience no weight loss and up to 50% leave the hospital with residual congestion. Patients with residual congestion and minimal weight loss at hospital discharge experience a disproportionately high number of readmissions. Up to 20% of hospitalized patients have a poor initial response to IV loop diuretics, and are considered diuretic “non- responsive”. As a result of untreated fluid and sodium retention, worsening heart failure (WHF) occurs frequently during their inpatient stay. Patients who develop WHF experience prolonged hospital lengths of stay (LOS), increased mortality, and consume significantly more resources. There is an unmet need to individualize diuretic therapy to improve decongestion and subsequently reduce adverse events. Yet, even knowing the fundamental role of congestion in AHF, there is little consensus among clinicians about how to optimize diuretic responsiveness. Despite multiple clinical trials aiming to clarify the ideal approach to loop diuretics in the management of congestion, the appropriate selection of dose and route, as well as determination of effectiveness of diuretic therapy remains largely empirical. A standardized, protocol-driven treatment pathway for hospitalized patients started in the first two hours of ED evaluation and utilizing objective measures of diuretic response is needed. This would maximize diuretic efficiency, facilitate quicker resolution of congestion, avoid WHF and prolonged LOS, and reduce AHF readmissions. Our strong preliminary data suggests low urine sodium predicts length of stay and outcomes after initial diuretic dosing in the outpatient and inpatient setting, and can be used to titrate diuretics. Our preliminary use of spot urine sodium to titrate loop diuretic doses and maximize response in inpatients with AHF has shown compelling improvements in congestion and weight loss. We propose to begin this protocol in the ED and hypothesize it will improve AHF outcomes relative to structured guideline-based usual care. Specifically, we hypothesize use of spot urine guided diuretic therapy will: 1) result in significant improvement in global clinical status at 5 days relative to structured guideline-based usual care, and 2) result in significant improvement in congestion at 5 days and in global rank at 30 days relative to structured guideline-based usual care. Early protocolized treatment of patients with AHF will more rapidly improve dyspnea, avoid development of in-hospital WHF, result in greater decongestion at hospital discharge, and therefore prevent HF-related readmissions and CV death.

摘要 在因急性心力衰竭（AHF）住院的一百万急诊科（艾德）患者中， 利尿剂是超过80%时间使用的唯一IV治疗，尽管证据等级仅为C。之前 研究集中在IV利尿剂的初始剂量上，并且未能找到具有最大功效的策略。 利尿剂剂量和反应差异很大，导致许多患者治疗不充分。有些人有临床 对利尿剂治疗有反应，导致症状改善，并在3 - 5天内出院 天然而，尽管有明显的症状改善，50%的患者没有体重减轻， 高达50%的患者在离开医院时仍有残余充血。残留充血和体重最低的患者 在出院时损失经历了不成比例的高的再入院次数。高达20%的 住院患者对IV袢利尿剂的初始反应较差，被认为是利尿剂"非- 响应"。由于未经治疗的液体和钠潴留，发生心力衰竭恶化（WHF） 经常在住院期间。发生WHF的患者住院时间延长 (LOS)死亡率增加，消耗更多的资源。有一个未满足的需求， 利尿剂治疗，以改善缓解充血，并随后减少不良事件。然而，即使知道 充血在AHF中的基本作用，临床医生对如何优化 利尿反应性。尽管多项临床试验旨在阐明髓袢利尿剂的理想方法， 充血的管理，剂量和途径的适当选择，以及 利尿剂治疗的有效性在很大程度上仍然是经验性的。标准化、方案驱动的治疗途径 对于在艾德评价的前两个小时开始的住院患者， 需要利尿反应。这将最大限度地提高利尿效率，促进更快地解决充血， 避免WHF和延长的LOS，并减少AHF再入院。我们强劲的初步数据表明， 尿钠可预测门诊和住院患者首次利尿剂给药后的住院时间和预后 设置，并可用于滴定利尿剂。我院初步应用点滴尿钠滴定袢利尿剂 剂量和最大限度的反应，在住院病人与AHF已显示出引人注目的改善充血， 减肥.我们建议开始在艾德实施该方案，并假设它将改善AHF的结局， 结构化的基于指南的常规护理。具体来说，我们假设使用点尿指导利尿治疗 将：1）相对于基于结构化指南的治疗，5天时总体临床状态显著改善 常规护理，以及2）在第5天时导致充血显著改善，在第30天时导致全球排名显著改善 相对于基于结构化指南的常规护理。AHF患者的早期方案化治疗将更多地 迅速改善呼吸困难，避免院内WHF的发展，导致在医院更好地缓解充血 出院，从而预防HF相关再入院和CV死亡。