Scientific and logistical challenges in designing the CONTROL trial: Recombinant factor VIIa in severe trauma patients with refractory bleeding

Background Clinical research in trauma patients poses multiple challenges in study design. These reflect the heterogeneity of injury and treatment, the paucity of acceptable study endpoints aside from mortality, and the difficulties inherent in obtaining informed consent in acutely ill populations. A current example of this problem is the study of recombinant factor VIIa (rFVIIa), which has attracted considerable interest as a systemic procoagulant agent for use in trauma patients with exsanguinating hemorrhage.Purpose To report on the implementation of an international trial — CONTROL — intended to assess the efficacy and safety of rFVIIa in trauma, and discuss trauma research study design in light of this experience.Methods The CONTROL trial international steering committee confronted a number of barriers in the design of the CONTROL trial. They addressed methodologies for (1) standardizing entry criteria for trauma patients suffering inherently heterogeneous injuries, (2) obtaining informed consent in ...