Balanced resuscitation and earlier mortality end points: bayesian post hoc analysis of the PROPPR trial

INTRODUCTION: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial failed to demonstrate a mortality difference for hemorrhaging patients receiving a balanced (1:1:1) vs a 1:1:2 resuscitation at 24 hours and 30 days. Recent guidelines recommend earlier mortality end points for hemorrhage-control trials, and the use of contemporary statistical methods. The aim of this post hoc analysis of the PROPPR trial was to evaluate the impact of a balanced resuscitation strategy at early resuscitation time points using a Bayesian analytical framework. METHODS: Bayesian hierarchical models were created to assess mortality differences at the 1, 3, 6, 12, 18, and 24 hours time points between study cohorts. Posterior probabilities and Bayes factors were calculated for each time point. RESULTS: A 1:1:1 resuscitation displayed a 96%, 99%, 94%, 92%, 96%, and 94% probability for mortality benefit at 1, 3, 6, 12, 18, and 24 hours, respectively, when compared with a 1:1:2 approach. Associated Bayes factors for each respective time period were 21.2, 142, 14.9, 11.4, 26.4, and 15.5, indicating ‘strong’ to ‘decisive’ supporting evidence in favor of balanced transfusions. CONCLUSION: This analysis provides evidence in support that a 1:1:1 resuscitation has a high probability of mortality benefit when compared with a 1:1:2 strategy, especially at the newly defined more proximate time points during the resuscitative period. Researchers should consider using Bayesian approaches, along with more proximate end points when assessing hemorrhage-related mortality, for the analysis of future clinical trials. LEVEL OF EVIDENCE: Level III/Therapeutic.