Statistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial

Abstract

Background: ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes. Objective: To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial. Methods: We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes. Conclusion: According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study’s reported results.