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Importance: Decision-making in trauma patients remains challenging and often results in deviation from guidelines. Machine-Learning (ML) enhanced decision-support could improve hemorrhage resuscitation. Aim: To develop a ML enhanced decision support tool to predict Need for Hemorrhage Resuscitation (NHR) (part I) and test the collection of the predictor variables in real time in a smartphone app (part II). Design, setting, and participants: Development of a ML model from a registry to predict NHR relying exclusively on prehospital predictors. Several models and imputation techniques were tested. Assess the feasibility to collect the predictors of the model in a customized smartphone app during prealert and generate a prediction in four level-1 trauma centers to compare the predictions to the gestalt of the trauma leader. Main outcomes and measures: Part 1: Model output was NHR defined by 1) at least one RBC transfusion in resuscitation, 2) transfusion ≥ 4 RBC within 6 h, 3) any hemorrhage control procedure within 6 h or 4) death from hemorrhage within 24 h. The performance metric was the F4-score and compared to reference scores (RED FLAG, ABC). In part 2, the model and clinician prediction were compared with Likelihood Ratios (LR). Results: From 36,325 eligible patients in the registry (Nov 2010—May 2022), 28,614 were included in the model development (Part 1). Median age was 36 [25–52], median ISS 13 [5–22], 3249/28614 (11%) corresponded to the definition of NHR. A XGBoost model with nine prehospital variables generated the best predictive performance for NHR according to the F4-score with a score of 0.76 [0.73–0.78]. Over a 3-month period (Aug—Oct 2022), 139 of 391 eligible patients were included in part II (38.5%), 22/139 with NHR. Clinician satisfaction was high, no workflow disruption observed and LRs comparable between the model and the clinicians. Conclusions and relevance: The ShockMatrix pilot study developed a simple ML-enhanced NHR prediction tool demonstrating a comparable performance to clinical reference scores and clinicians. Collecting the predictor variables in real-time on prealert was feasible and caused no workflow disruption. [ABSTRACT FROM AUTHOR]