Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Trial is an innovative Bayesian, phase 2b, randomized clinical trial. The goal of the trial, which is funded by the American Heart Association and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is to explore the efficacy of early prophylaxis against catheter-associated deep venous thrombosis in critically ill children. The trial is being conducted in the pediatric intensive care units at Yale-New Haven Children’s Hospital, St. Louis Children’s Hospital, Dell Children’s Medical Center of Central Texas, Children’s Hospital of Wisconsin, Maria Fareri Children’s Hospital, and Golisano Children’s Medical Center.
Catheter-associated thrombosis is a significant problem in critically ill children. It occurs in 18% of children with untunneled central venous catheters and is associated with prolonged stay in the intensive care unit, increased risks of bloodstream infection, pulmonary embolism, and mortality, and increased costs of care. Despite the adverse outcomes, prophylaxis is not recommended in children because of the absence of pediatric data on its efficacy in preventing catheter-associated thrombosis. Given the differences in the hemostatic system between children and adults, the recommendation to provide prophylaxis in critically ill adults should not be applied routinely to children.
In the CRETE Trial, enoxaparin will be administered to critically ill children within 24 hours of insertion of an untunneled central venous catheter. The dose of enoxaparin will be adjusted to a target anti-Xa level. Ultrasound will be done once the catheter is removed to obtain preliminary evidence on the effect of early prophylaxis on the incidence of catheter-associated thrombosis. In addition, endogenous thrombin potential will be measured from plasma to evaluate the effect of the anti-Xa activity-directed prophylactic strategy on thrombin generation.
The CRETE Trial will determine whether a phase 3 trial of early prophylaxis against catheter-associated deep venous thrombosis in critically ill children should be conducted. It will also determine the appropriate dose of enoxaparin for this phase 3 trial.