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.

抽象的 在有急性心力衰竭（AHF）住院的一百万急诊科（ED）患者中 利尿剂是80％以上使用的唯一静脉治疗，尽管只有证据。 研究集中于初始剂量的利尿剂，未能以最大效率找到一种策略。 利尿剂给药和反应差异很大，使许多患者接受治疗不足。有些有临床 对利尿治疗的反应，导致3-5内医院的症状改善和出院 天。但是，多皮特症状的改善，这些患者中有50％没有体重减轻， 多达50％的人离开医院残留充血。残留充血和最小体重的患者 出院出院的损失经历了不成比例的再入院次数。最多20％ 住院的患者对静脉循环利尿剂的初始反应较差，被认为是利尿 响应迅速”。由于未处理的液体和钠保留率，令人担忧的心力衰竭（WHF）发生 经常在住院期间。发展WHF的患者长期住院时间 （LOS），死亡率增加，并消耗更多的资源。有个性化的需求 利尿治疗可改善断裂并随后减少不良事件。但是，即使知道 拥塞在AHF中的基本作用，临床医生在如何优化方面几乎没有共识 利尿反应能力。尽管进行了多项临床试验，旨在阐明理想的循环利尿剂方法 交通拥堵的管理，适当的剂量和路线选择以及确定 利尿治疗的有效性在很大程度上仍然是经验性的。标准化，协议驱动的治疗途径 对于住院的患者，在ED评估的前两个小时开始，并利用了客观的措施 需要利尿反应。这将最大程度地提高利尿效率，促进更快地解决拥塞， 避免使用WHF并延长LOS，并减少AHF再入院。我们强大的初步数据表明低 尿钠预测在门诊和住院患者初始利尿剂给药后的住院时间和结果长度 设置，可以用来用于提示利尿剂。我们初步使用点尿液钠来递减循环利尿剂 剂量和最大化AHF住院患者的反应已显示出充血和 我们建议在ED中开始此协议，并假设它将改善AHF结果相对 基于结构化指南的常规护理。具体而言，我们假设使用点尿引导的利尿治疗 意志：1）相对于基于结构化指南 通常的护理和2）在5天时的交通拥堵并在30天达到全球排名 相对于基于结构化指南的常规护理。早期协议对AHF患者的治疗将更多 迅速改善呼吸困难，避免发生院内WHF，导致医院更大 出院，因此可以防止与HF相关的再入院和CV死亡。