A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Frailty’s influence on 30-day mortality in old critically ill ICU patients: a bayesian analysis evaluating the clinical frailty scale

“…An absolute difference of 10% over the baseline event rate of 40% for the primary endpoint, 30-day mortality, was considered as the MCID (which results in an odds ratio of approximately 1.5). Therefore, the margin for a large effect was set as 1.5 × above 1.84 as previously suggested [ 15 ].…”

Debate: Intermittent Hemodialysis versus Continuous Kidney Replacement Therapy in the Critically Ill Patient: The Argument for CKRT

“…17,72 These estimates are improbably large and well beyond what would be considered a realistic minimal clinically important difference. 73 Trials that compared CKRT and intermittent HD had other methodological challenges that may compromise the interpretation of results. These include differences in baseline characteristics after randomization, 17 exclusion postrandomization, 64,68 and compromised generalizability because of clinician refusal to enroll, exclusion of patients with hemodynamic instability, or inclusion of patients with low acuity of illness.…”

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults

“… 23 Multiple randomized trials in adults evaluating the effect of timing of initiation on CRRT outcomes have yielded conflicting results. 14 , 15 , 24 , 25 , 26 , 27 , 28 , 29 In children, there are no randomized trials evaluating the timing of CRRT initiation and outcomes, and most studies are small, single center in design with varied timing definitions. 11 , 12 , 30 , 31 , 32 , 33 Therefore, a similar controversy as to the optimal timing of CRRT initiation in children exists.…”