REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury (RELIEVE-AKI)

急性肾损伤（RELIEVE-AKI）体外容量去除评估的限制性与自由性比率

• 批准号: 10364868
• 负责人: Kianoush B Kashani
• 金额: $ 32.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364868
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Antihypertensive Agents; Arrhythmia; Blood flow; Cardiac; Caring; Cessation of life; Clinical Practice Guideline; Clinical Trials; Cluster randomized trial; Critical Care; Critical Illness; Dependence; Diabetes Mellitus; Dialysis procedure; Digestive System Disorders; Evaluation; Excision; Fluid overload; Goals; Health; Hemodialysis; Hospital Mortality; Hospitals; Hour; Hypotension; Injury; Injury to Kidney; Institutes; Intensive Care Units; Kidney Diseases; Kidney Failure; Knowledge; Length of Stay; Liquid substance; Measures; Mechanical ventilation; Mission; Morbidity - disease rate; Multi-Institutional Clinical Trial; Myocardial Ischemia; Observational Study; Organ; Outcome; Outpatients; Patient Recruitments; Patient-Focused Outcomes; Patients; Phase; Physicians; Population; Positioning Attribute; Pragmatic clinical trial; Protocols documentation; Randomized; Randomized Clinical Trials; Renal Replacement Therapy; Renal function; Residual state; Risk; System; Time; Ultrafiltration; Unit of Measure; Work; adherence rate; clinical center; clinical practice; comparative effectiveness; design; effective therapy; evidence base; experience; improved; improved outcome; mortality; mortality risk; patient oriented; pragmatic trial; randomized trial; recruit; response; safety outcomes; secondary analysis; secondary outcome; therapy design; treatment arm; treatment group

Abstract Two-thirds of critically ill patients with acute kidney injury have a fluid overload at the time of initiation of kidney replacement therapy in the intensive care unit. Although “net ultrafiltration (UFNET),” also known as net fluid removal during kidney replacement therapy, has been used in the treatment of fluid overload for more than seven decades, the optimal rate of UFNET remains uncertain, complications such as hypotension and cardiac arrhythmias occur frequently, and more than 40% of critically ill patients die. Emerging evidence from observational studies suggests a “J” shaped association between UFNET rate and mortality in critically ill patients with acute kidney injury and treated with kidney replacement therapy. Higher UFNET rates are associated with an increased risk of death compared with moderate and lower UFNET rates. Understanding the causal effects of UFNET rate on outcomes is critical to design interventions to reduce mortality, develop evidence-based clinical practice guidelines, and implement quality measures for UFNET. In the absence of such knowledge, optimizing UFNET to improve outcomes will remain problematic. Thus, we will conduct a pilot clinical trial entitled REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury (RELIEVE-AKI) to examine the feasibility of restrictive compared with a liberal UFNET rate strategy. The study is a stepped-wedge cluster-randomized trial involving 144 critically ill patients with acute kidney injury and treated with continuous kidney replacement therapy in six intensive care units across two hospital systems. The intensive care units will be randomized 1:1 in which patients will receive either a restrictive or a liberal UFNET rate strategy. Both strategies are standards of care and are commonly used in current clinical practice. In the restrictive group, the UFNET rate will be titrated and maintained between 0.5-1.5 mL/kg/h. In the liberal group, the UFNET rate will be titrated and maintained between of 2.0-5.0 mL/kg/h. The primary feasibility outcomes are between-group differences in patient mean delivered UFNET rates, protocol adherence, and rate of patient recruitment (Aim 1). We will also explore the effects of alternative UFNET rate strategies on secondary outcomes including hypotensive episodes, and cardiac arrhythmias; emergent use of rescue UFNET rates higher than the assigned treatment arm for fluid overload; duration of kidney replacement therapy and mechanical ventilation; intensive care unit and hospital length of stay, and independence from kidney replacement therapy and hospital mortality (Aim 2). This pragmatic clinical trial will be used to support the rationale, assess feasibility, and design a phase III multicenter randomized trial to examine the effects of alternative UFNET rate strategies on patient-centered clinical outcomes. Our study will have a direct impact on the care of critically ill patients with acute kidney injury and thus will influence clinical practice, physicians, and policymakers.

抽象的 三分之二的急性肾损伤危重患者在开始肾移植时存在液体超负荷 重症监护室的替代疗法 虽然“净超滤（UFNET）”也称为净液。 在肾脏替代治疗期间去除，已用于治疗液体超负荷超过 七十年来，UFNET的最佳速率仍不确定，低血压和心脏病等并发症 心律失常频繁发生，超过 40% 的重症患者死亡。 观察性研究表明，UFNET 率与重症患者死亡率之间存在“J”形关联 患有急性肾损伤并接受肾脏替代治疗的患者 UFNET 率较高。 与中等和较低的 UFNET 率相比，死亡风险增加相关。 UFNET 率对结果的因果影响对于设计干预措施以降低死亡率、制定 基于证据的临床实践指南，并在缺乏此类指南的情况下实施 UFNET 的质量措施。 知识，优化 UFNET 以改善结果仍然存在问题，因此，我们将进行试点临床。 题为“急性肾损伤中体外体积清除率的限制性与自由性评估”的试验 (RELIEVE-AKI) 旨在检验限制性 UFNET 利率策略与自由主义 UFNET 利率策略相比的可行性。 一项阶梯楔形整群随机试验，纳入了 144 名接受治疗的急性肾损伤危重患者 在两个医院系统的六个重症监护病房进行持续的肾脏替代治疗。 重症监护病房将以 1:1 的比例随机分配，患者将接受限制性或自由性 UFNET 这两种策略都是护理标准，并且在当前的临床实践中常用。 限制性组中，UFNET 速率将滴定并维持在 0.5-1.5 mL/kg/h 之间。 UFNET 速率将逐步调整并维持在 2.0-5.0 mL/kg/h 之间。 主要可行性结果为 患者平均 UFNET 率、方案依从性和患者率的组​​间差异 我们还将探讨替代 UFNET 费率策略对中学的影响。 结果包括低血压发作和心律失常的紧急使用救援 UFNET 率； 高于指定的液体超负荷治疗组；以及 机械通气；重症监护室和住院时间以及独立于肾脏的情况 替代疗法和医院死亡率（目标 2）。 理由、评估可行性并设计 III 期多中心随机试验来检验其效果 我们的研究将对以患者为中心的临床结果产生直接影响。 急性肾损伤危重患者的护理，从而影响临床实践、医生和 政策制定者。