Smith Orla M, Wald Ron, Adhikari Neill K J, Pope Karen, Weir Matthew A, Bagshaw Sean M
Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, 3C1,12 Walter C, Mackenzie Centre, 8440-112 St, Edmonton, NW RILF3 T6G2B7, Canada.
Trials. 2013 Oct 5;14:320. doi: 10.1186/1745-6215-14-320.
Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation.
METHODS/DESIGN: This is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ≥6.0 mmol/L; serum bicarbonate ≤10 mmol/L; severe respiratory failure (PaO₂/FiO₂<200) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events).
The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial.
NCT01557361.
急性肾损伤是危重病常见且严重的并发症，严重病例常需肾脏替代治疗。虽然最近一项系统评价表明“更早”开始肾脏替代治疗可提高生存率，但已完成的试验因样本量小、单中心性质以及使用不同定义来界定“早期”肾脏替代治疗开始时间而受到限制。
方法/设计：这是一项开放标签的试点随机对照试验。100例患有严重急性肾损伤的危重病患者将按1:1随机分配，在加拿大12个中心接受“加速”开始肾脏替代治疗或“标准”开始治疗。在加速组中，参与者将放置静脉导管，并在符合条件后12小时内开始肾脏替代治疗。在标准开始组中，参与者将接受7天的监测以确定肾脏替代治疗的指征。对于标准组中持续存在急性肾损伤（定义为血清肌酐较符合条件时的值下降未超过50%）的参与者，除非满足以下一项或多项标准，否则不鼓励开始肾脏替代治疗：血清钾≥6.0 mmol/L；血清碳酸氢盐≤10 mmol/L；严重呼吸衰竭（动脉血氧分压/吸入氧分数值<200）或符合条件后持续急性肾损伤≥72小时。纳入标准旨在确定一群患有严重急性肾损伤的危重病成年患者，他们在住院期间可能需要肾脏替代治疗，但并非立即需要。主要结局是方案依从性（>90%）。次要结局包括可行性指标（纳入试验的符合条件患者比例、随访至90天以评估生命状态和肾脏替代治疗需求的纳入患者比例）和安全性（不良事件的发生情况）。
严重急性肾损伤患者开始肾脏替代治疗的最佳时机仍不确定，这是一个重要的知识空白，也是高质量研究的重点。这项试点试验对于确定方案可行性、确认参与者安全性以及为大型确定性试验设计获取估计事件发生率是必要的。
NCT01557361。
