Grant: Project Grant

In patients undergoing cardiac surgery, both red blood cell (RBC) transfusion and anemia are associated with an increased risk for morbidity and mortality; and the point at which the risks associated with anemia and transfusion are balanced remains undefined. We recently published the results of our TRICS III trial in the New England Journal of Medicine, where we demonstrated non-inferiority of a restrictive RBC transfusion strategy compared to a liberal strategy with respect to a composite outcome of death, heart attack, stroke, or new-onset renal failure with dialysis in adults undergoing cardiac surgery on cardiopulmonary bypass. Hypothesis generating subgroup analyses from TRICS III demonstrated a significant interaction between transfusion threshold and age, whereby the liberal strategy appeared to be better than the restrictive strategy in patients <75 years of age. The interaction was robust in a series of sensitivity analyses, with the age at which the differences become manifest around 65. However, in the absence of other randomized controlled trial evidence, it remains unknown which transfusion strategy is preferable in these patients. To address this, we will conduct the TRICS IV study, which is a multi-center open-label randomized controlled trial of a restrictive versus liberal transfusion strategy in high risk patients under 65 years of age having cardiac surgery, using a superiority trial design. The study will incorporate an innovative pragmatic and adaptive design. The results from TRICS IV will provide definitive evidence to determine whether a liberal strategy is better than a restrictive one in younger patients. Irrespective of the results, such information is likely to be of high impact for transfusion practice in cardiac surgery around the world, with significant potential implications for all patients undergoing surgical procedures.