Zampieri Fernando G, Serpa-Neto Ary, Wald Ron, Bellomo Rinaldo, Bagshaw Sean M
Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Alberta, Canada.
Department of Intensive Care, Austin Hospital, Melbourne, Australia.
J Crit Care. 2024 Aug;82:154767. doi: 10.1016/j.jcrc.2024.154767. Epub 2024 Mar 11.
To perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR).
All patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy - RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis.
The WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96-1.13; p = 0.33) and 1.02 (95% CI; 0.90-1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79-0.99; p = 0.03) and 1.02 (95% CI; 0.87-1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial.
WR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation.
ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL).
通过使用胜率（WR）的分层复合终点分析，对急性肾损伤中肾脏替代治疗的标准启动与加速启动（STARRT - AKI）试验以及危重症患者持续性肾脏替代治疗强度（RENAL）试验进行事后重新分析。
选取来自STARRT - AKI试验（比较肾脏替代治疗 - RRT启动的加速与标准方法）和RENAL试验（比较危重症患者两种不同RRT剂量）且信息完整的所有患者。WR被定义为一个分层复合终点，使用90天死亡率、90天时的RRT依赖、重症监护病房（ICU）住院时长（LOS）和医院住院时长（主要分析）；单位以上的值表示该干预措施对分层复合终点有益。进行了一项次要分析，用存活且无需RRT的天数替代LOS。根据疾病严重程度评分、手术状态和脓毒症的存在情况进行分层分析。
WR分析分别为STARRT - AKI试验产生了2,141,830对数据，为RENAL试验产生了536,446对数据。STARRT - AKI和RENAL试验主要分析的WR结果分别为1.04（95%置信区间[CI] 0.96 - 1.13；p = 0.33）和1.02（95% CI；0.90 - 1.15；p = 0.75），次要分析的结果分别为0.88（95% CI；0.79 - 0.99；p = 0.03）和1.02（95% CI；0.87 - 1.21；p = 0.77）。主要分析的分层分析表明，在STARRT - AKI试验中，加速策略可能对非手术脓毒症患者有益，而次要分析表明，加速策略可能对无脓毒症的手术患者有害。RENAL试验的分层分析中没有治疗效果异质性的证据。
使用分层复合终点的WR方法对于危重症肾脏病学试验是可行的。STARRT - AKI和RENAL试验的主要重新分析均得出中性结果；然而，在STARRT - AKI试验按手术状态和脓毒症进行的分层分析中，有治疗效果异质性的迹象。在试验设计前使用WR方法选择终点和分层顺序对试验解释可能有重要影响。
ClinicalTrials.gov编号NCT02568722（STARRT - AKI）和NCT00076219（RENAL）。
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