PROJECT SUMMARY This U34 application is for the planning of a future clinical trial “Trauma Resuscitation with Group O Whole Blood Or Products” (TROOP). The overarching aims of this proposal are to mature the statistical design of the TROOP trial, and to develop the research infrastructure required to carry out the trial. Our efforts will be complemented by guidance and input from the NIH Innovative Clinical Trials Resource. These efforts will lead to a future NIH application to support a large multicenter clinical trial. Bleeding (hemorrhage) is the most common cause of preventable death after injury. Treatment of bleeding requires both surgery (to stop the bleeding) and replacement of lost blood. In order to allow donated blood to serve multiple patients, modern blood banking practices separate donor blood into multiple components (red blood cells, plasma, and platelets). However, severely injured patients require all of these components. Military experience during the wars in Iraq and Afghanistan have innovated the use of whole unseparated blood in resuscitation of hemorrhagic shock. While simpler and potentially more effective than separated blood products, the benefit of whole blood or component blood in the setting of hemorrhage shock is unknown. We aim to carry out a multicenter clinical trial (TROOP) comparing whole blood vs conventional separated component blood in the resuscitation of traumatic hemorrhagic shock. We propose to use a Bayesian group- sequential design for this study, which makes better use of existing information, requires fewer patients, and provides answers more quickly. Bayesian designs are innovative, but also more complex, and require more planning and preparation than conventional trials. We also plan to incorporate a cost-effectiveness analysis to assess the value of the interventions. Key tasks during the planning phase will include refinement of the Bayesian design, elicitation of expert opinion to support Bayesian prior probability estimates, collection of baseline cost data, recruitment of hospitals to participate in the trial, development of data collection infrastructure, interface with the Food and Drug Administration, and development of the clinical trial protocol. The TROOP trial will entail a collaborative effort between the University of Alabama at Birmingham, and the University of Texas Health Science Center at Houston. The effort will unite experts in trauma surgery, critical care, emergency medicine, biostatistics, health economics, and trials methodology. The knowledge gained from the TROOP trial would directly impact civilian and military trauma care, identifying the optimal approach to blood transfusion therapy in severely injured patients.

RELEVANCE Bleeding (hemorrhage) is the most common cause of preventable death after injury, and blood transfusion is one of the cornerstones of treatment. This U34 application is for the planning and design of a future clinical trial “Trauma Resuscitation with Group O Whole Blood Or Products” (TROOP). The trial will determine whether the transfusion of whole blood, as opposed to component therapy, is associated with improved survival, and whether it is cost-effective.