OBJECTIVE: To determine bivalirudin’s safety, plasma concentration (PK), pharmacodynamics (PD), and dosing guidelines when used as a procedural anticoagulant in pediatric percutaneous intravascular procedures using the dose for adults undergoing PCI (0.75 mg/kg bolus, followed by a 1.75 mg/kg/hr infusion)
METHODS: This is a prospective, open-label, single-arm, multicenter, non-randomized trial. 110 patients were enrolled, 50% received a device (ASD, PDA, stent, coil), 50% had balloon angioplasty & valvuloplasty or diagnostic procedures. There were 11 neonates, 33 infants/toddlers, 32 young children, and 34 older children. End-points were: bleeding (major & minor), and thrombotic events.
RESULTS: Drug concentration (PK) was higher in older children. The half-life was consistent with adult times. Drug clearance and volume of distribution increased with weight and age. PD: ACT levels are comparable post-dose between neonates and older children/adults. Weight based (mg/Kg) dosing provides a lower drug concentration in neonates compared to older children/adults. End-points : Thrombosis and major bleeding events at 30 days were 8.2% and 1.8% respectively. All but one of the thrombosis events were sheath clots. Two major bleeds, both hematomas > 2.5 cm, two patients treated for decreased pulses(1.8%).

CONCLUSION: 1) Bivalirudin provided safe anticoagulation in all age groups. Major bleeding occurred in 1.8% of patient population. For the older age (>2 yrs) categories, PK appears to be consistent with adult data. For neonates, weight-based dose results in lower PK, but anticoagulation did occur at that dose. Although end point definitions were sensitive in this study, they are comparable to published events using heparin.