Abstract 2208: Optimal Dose of Clopidogrel for Platelet Inhibition in Children: Primary Results of the PICOLO Trial
Background: Children with certain types of congenital heart disease (CHD) are at increased risk for thrombotic complications. Clopidogrel is an ADP platelet antagonist widely used in adults at a dose of 75 mg/day to safely prevent thrombotic events. The optimal dose to achieve similar platelet inhibition in children is unknown.
Methods: We performed the first prospective, international, multi-center randomized placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 –24 months) with CHD at risk for thrombosis. The primary objective was to determine the optimal dose of clopidogrel to achieve a mean 30 –50% inhibition of 5 μM ADP-induced platelet aggregation (i.e. inhibition similar to that seen with 75 mg (~1 mg/kg) in adults). A second objective was to assess the safety and tolerability of clopidogrel. Platelet aggregation was assessed at baseline and steady-state (7–28 days of treatment) by light transmission aggregometry with central core lab assessment of tracings. Patients were randomized to clopidogrel vs placebo in a 3:1 ratio in 4 sequential groups: 0.01, 0.10, 0.15, and 0.20 mg/kg for ≥7 days up to 28 days.
Results: In total, 116 patients were enrolled at 20 centers; 92 (50% neonates; 50% infants) were randomized and 73 completed the dosing regimen and pharmacodynamic sampling. A total of 78% were on aspirin; 71% had systemic to pulmonary artery shunts (31% with hypoplastic left heart syndrome) and 26% had vascular stents. The variability of % inhibition of platelet aggregation with clopidogrel was high (Table⇓). No bleeding or other adverse events were attributed to clopidogrel.
Conclusion: Clopidogrel is well tolerated in children. Clopidogrel 0.20 mg/kg/day in children aged 0 –24 months achieves a platelet inhibition level similar to that in adults taking 75 mg/day.