Thromboembolic disease is an increasingly significant complication occurring in children usually as a result of technologic advances and the improved survival of children with serious underlying disorders. Currently, children with thrombosis are treated with so- called standard anticoagulants, mostly heparin, low molecular weight heparins, and oral vitamin K antagonists. There are significant limitations to these agents which are accentuated in children. Several new anticoagulants have recently been approved for a variety of indications in adults. These agents have improved properties over the standard anticoagulants and have been shown to be safer and more efficacious in adults leading to their approval by the Food &Drug Administration. One of these agents, bivalirudin, a direct thrombin inhibitor has been shown to be safe and effective in a study of infants less than 6 months of age, however this agent, while promising, has not been studied in older infants and children.
The aim of this study is to assess the safety, efficacy, dosing and pharmacokinetics of bivalirudin in children between 6 months and 18 years of age who have an acute deep vein thrombosis. The study will utilize the initial dosing shown to be effective in the infant study (0.125 mg/kg bolus followed by an infusion of 0.125 mg/kg/hour). Dose adjustments will be based on the activated partial thromboplastin time (aPTT) which will be the pharmacodynamic (PD) parameter measured. Pharmacokinetics (PK) will also be assessed by measuring plasma bivalirudin levels and correlation of the PD to the PK parameter will be performed. The study will also assess safety by evaluating for bleeding, specifically, as well as other adverse events. In addition, the study will assess efficacy by re-evaluating the thrombus at 48-72 hours as well as continued efficacy by re-evaluating the thrombus at ~30 days after study drug initiation. This project supports the mission of the Orphan Product Drugs Division by evaluating a potentially safe and effective medication (and potentially safer and more effective) in a vulnerable population for a rare condition. Public Health Relevance: Thrombosis is a significant medical complication in children with chronic diseases. The currently utilized treatments have many drawbacks which can lead to poor outcomes. More modern therapies are available but have not been systematically tested in children. This study will determine whether one such medication, bivalirudin is a safer and more effective alterative.
Thrombosis is a significant medical complication in children with chronic diseases. The currently utilized treatments have many drawbacks which can lead to poor outcomes. More modern therapies are available but have not been systematically tested in children. This study will determine whether one such medication, bivalirudin is a safer and more effective alterative.
| Young, Guy (2017) How I treat pediatric venous thromboembolism. Blood 130:1402-1408 |
| O'Brien, S H; Yee, D L; Lira, J et al. (2015) UNBLOCK: an open-label, dose-finding, pharmacokinetic and safety study of bivalirudin in children with deep vein thrombosis. J Thromb Haemost 13:1615-22 |
