Academic Research Organization, Albert Einstein Hospital, São Paulo, Brazil.
Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, 2-124E Clinical Sciences Building, 8440-112 St NW, Edmonton, AB, T6G2B7, Canada.
Crit Care. 2022 Aug 25;26(1):255. doi: 10.1186/s13054-022-04120-y.
Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework.
We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero-one inflated beta regression.
The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] - 3.30%; 3.40%], - 0.39% [95% CrI - 3.46%; 3.00%], and 0.64% [95% CrI - 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of - 3.55 days [95% CrI - 6.38; - 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI - 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66.
In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.
危重症患者开始肾脏替代治疗(KRT)的时机仍存在争议。标准与加速急性肾损伤肾脏替代治疗启动(STARRT-AKI)试验比较了危重症急性肾损伤患者两种 KRT 启动策略(加速与标准),结果显示 90 天全因死亡率无差异。对试验终点进行概率探索可能有助于更好地理解试验结果。我们旨在使用贝叶斯框架进行重新分析。
我们对来自多国 STARRT-AKI 试验的 2927 例随机患者进行了二次分析,该试验在 15 个国家的 168 个中心进行。主要终点为 90 天全因死亡率,采用分层贝叶斯逻辑回归进行评估。一系列先验概率包括乐观、中性和悲观先验概率,以及来自早期临床试验的先验概率。次要终点(无 KRT 天数和无住院天数)采用零一膨胀贝塔回归进行评估。
使用贝叶斯逻辑回归对主要终点进行分析后,与标准 KRT 启动策略相比,加速 KRT 启动策略的后验获益概率提示无显著差异,无论使用何种先验概率(绝对差值分别为 0.13%[95%可信区间(CrI)-3.30%;3.40%]、-0.39%[95% CrI-3.46%;3.00%]和 0.64%[95% CrI-2.53%;3.88%],分别对应中性、乐观和悲观先验概率)。该效应大小等于或大于共识定义的最小临床重要差异的可能性非常低。接受加速策略的患者无 KRT 天数更少(中位数绝对差值为-3.55 天[95% CrI-6.38;-0.48]),且接受加速策略更可能获得更多无 KRT 天数的概率为 0.008。两种策略的无住院天数相似,与标准策略相比,加速策略的无住院天数中位数绝对差值为 0.48 天(95% CrI-1.87;2.72),接受加速策略的可能性为 0.66。
在 STARRT-AKI 试验的贝叶斯重新分析中,我们发现与标准策略相比,加速策略具有重要临床获益的可能性非常低。接受加速策略的患者可能存活天数和无 KRT 天数更少。这些发现不支持采用加速 KRT 启动策略。