Abstract 13384: Cangrelor Pk / Pd Analysesin Neonates After Palliation of Congenital Heart Disease (chd)

Abstract

Background: Thrombotic events contribute significantly to early mortality in neonates with CHD requiring a systemic-to-pulmonary artery shunt. However, thromboprophylaxis remains suboptimal with few pharmacological agents studied and shown to be of benefit. The P2Y 12 inhibitor cangrelor is effective in preventing early coronary artery stent thrombosis in adults. Cangrelor dosing and safety have yet to be established in neonates. Hypotheses: (1) Cangrelor administered by infusion will yield drug levels capable of inhibiting maximal platelet aggregation by > 90% without causing an increase in bleeding. (2) A novel microfluidic technology can yield robust results related to inhibition of thrombus formation using significantly less blood than for LTA. Methods: This IRB approved, prospective, open-label, single-arm study was conducted between January 2017 and August 2019. Cangrelor, 0.5 μg/kg/min (n=7) or 0.25 μg/kg/min (n=8), was administered intravenously 6-10h after placement of a systemic-to-pulmonary artery shunt (n=8), right ventricle-to-pulmonary artery shunt (n=6), or ductal stent (n=1) for 1h. Plasma levels and PD properties of cangrelor were determined, the latter by light transmission aggregometry (LTA) and microfluidic assay (MFA). Informed consent was obtained (NCT02765633). Results: 15 participants that received cangrelor had single ventricle physiology (12 of 15) and underwent a Norwood procedure (11 of 15). Cangrelor 0.5 μg/kg/min dosing met all PD endpoints, yielding a higher level of platelet inhibition (mean ± SD) than the 0.25 μg/kg/min dose as assessed by LTA (89 ± 11.4% vs 73.3 ± 16.9%, respectively). Results from MF studies were comparable but required 3-fold less blood for testing. PK analysis revealed rapid drug clearance with 86.7% of participants having undetectable levels by 10 minutes post-infusion and 70% with full recovery in platelet function at 1 hour. SAEs and AEs that occurred were not related drug administration, including bleeding. Conclusion: Favorable PK and PD properties of cangrelor 0.5 μg/kg/min dosing and an acceptable safety profile warrant further evaluation in neonates following palliative cardiac procedures.