A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial
Fernando G. Zampieri, Bruno R. da Costa, Suvi T. Vaara, François Lamontagne, Bram Rochwerg, Alistair D. Nichol, Shay McGuinness, Danny F. McAuley, Marlies Ostermann, Ron Wald, Sean M. Bagshaw, STARRT-AKI Investigators, Sean M. Bagshaw, Ron Wald, Neill K. J. Adhikari, Rinaldo Bellomo, Didier Dreyfuss, Bin Du, Martin P. Gallagher, Stèphane Gaudry, François Lamontagne, Michael Joannidis, Kathleen D. Liu, Daniel F. McAuley, Shay McGuinness, Alistair D. Nichol, Marlies Ostermann, Paul M. Palevsky, Haibo Qiu, Ville Pettilä, Antoine Schneider, Orla M. Smith, Suvi T. Vaara, Matthew A. Weir, Rinaldo Bellomo, Glenn M. Eastwood, Leah Peck, Helen Young, Peter Krüger, Gordon Laurie, Emma Saylor, Jason Meyer, Ellen Venz, Krista Wetzig, Craig French, Forbes McGain, John Mulder, Gerard Fennessy, Sathyajith Koottayi, Samantha Bates, Miriam Towns, Rebecca Morgan, Anna Tippett, Andrew Udy, Chris Mason, Elisa Licari, Dashiell Gantner, Jason McClure, Alistair Nichol, Phoebe McCracken, Jasmin Board, Emma Martin, Shirley Vallance, Meredith Young, Chelsey Vladic, Steve McGloughlin, David Gattas, Heidi Buhr, Jennifer Coles, Debra Hutch, James Wun, Louise Cole, Christina Whitehead, Julie Lowrey, Kristy Masters, Rebecca Gresham, Victoria Campbell, David Gutierrez, Jane Brailsford, Loretta Forbes, Lauren Murray, Teena Maguire, Martina NiChonghaile, Neil Orford, Allison Bone, Tania Elderkin, Tania Salerno, Tim Chimunda, Jason Fletcher, Emma Broadfield, Sanjay Porwal, Cameron Knott, Catherine Boschert, Julie Smith, Angus Richardson, Dianne Hill, Graeme Duke, Peter Oziemski, Santiago Cegarra, Peter Chan
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.