ATHENA Trial

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Venous thromboembolism (VTE), composed mainly of deep venous thrombosis (DVT) and pulmonary embolism, is a top contributor to harm in hospitalized children. Critically ill adolescents are at high risk of VTE. Studies indicate that in addition to hypercoagulability, endothelial injury and venous stasis from central venous catheters are key determinants of DVT in critically ill adolescents. The appropriate strategy to prevent VTE in these adolescents is unknown. This results in wide variation in practice, low use of thromboprophylaxis, and increasing incidence of VTE in adolescents. Due to lack of pediatric-specific evidence, thromboprophylaxis practice in critically ill adolescents is extrapolated from adults. Pediatric patient safety initiatives recommend mechanical thromboprophylaxis (mTP) for these adolescents to account for the unique differences in the epidemiology of VTE in adolescents. Given the efficacy of pharmacological thromboprophylaxis (pTP) in adults, the pediatric initiatives recommend strongly considering combined mTP and pTP (mTP+pTP), which likely attenuates venous stasis from a central venous catheter and hypercoagulability. 

Yet, between mTP+pTP and mTP alone, the American Society of Hematology (ASH) in 2018 has suggested using mTP alone for medical inpatients because of uncertainty in the net clinical benefit of mTP+pTP with harm likely outweighing benefits. ASH identified as a high priority research need clinical trials that will provide evidence on the efficacy and harms of mTP+pTP vs mTP alone, particularly in high-risk medical inpatients. With the support of the PALISI Network, we have recruited over 40 pediatric intensive care units to conduct the Adjunctive THromboprophylaxis with Enoxaparin in iNtubated Adolescents (ATHENA) Trial and address this high priority research need. The central hypothesis is that mTP+pTP safely reduces the risk of VTE in critically ill adolescents over mTP alone. This innovative Bayesian adaptive, Goldilocks trial will randomize up to 400 adolescents with medical conditions and supported on invasive mechanical ventilation to receive either mTP with intermittent pneumatic compression device and pTP with subcutaneous enoxaparin, preferred agents in children, or mTP alone. Ultrasound will be performed upon discharge from the intensive care unit to diagnose DVT. Subjects will be followed for other VTE, bleeding events, heparin-induced thrombocytopenia, and pressure injury. Blood will also be collected to measure markers of hypercoagulability, venous stasis and endothelial injury. The ATHENA Trial addresses the high priority research need identified by ASH. It will provide much needed pediatric-specific evidence that will inform clinical practice. It will also enhance our understanding of the pathophysiology of VTE in critically ill adolescents.

Principal Investigator:
E. Vincent S. Faustino, MD, MHS
333 Cedar Street
New Haven, CT 06520
203-785-4651
vince.faustino@yale.edu