Title

Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial

UMMS Affiliation

Department of Pediatrics

Date

1-29-2008

Document Type

Article

Medical Subject Headings

Aspirin; Dose-Response Relationship, Drug; Hemorrhage; Humans; Infant; Infant, Newborn; Platelet Aggregation; Platelet Aggregation Inhibitors; Ticlopidine

Disciplines

Hematology | Oncology | Pediatrics

Abstract

BACKGROUND: Infants and young children with certain types of heart disease are at increased risk for thromboses. Clopidogrel 75 mg/d is used in adults to prevent thrombotic events. The dose to achieve similar platelet inhibition in children is unknown. The objectives of the present study were (1) to determine the dose of clopidogrel needed in infants and young children to achieve a mean 30% to 50% inhibition of 5-micromol/L ADP-induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and (2) to assess the safety and tolerability of clopidogrel in infants and young children.

METHODS AND RESULTS: We performed a prospective, multicenter, randomized, placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 to 24 months) with a cardiac condition at risk for arterial thrombosis. Patients were randomized to clopidogrel versus placebo in a 3:1 ratio in 4 sequential groups (0.01, 0.10, 0.20, and 0.15 mg/kg) for > or = 7 and andlt; or = 28 days. Platelet aggregation was assessed at baseline and steady state by light-transmission aggregometry. Of 116 patients enrolled, 92 (50% neonates, 50% infants/toddlers) were randomized, and 73 completed the study. A total of 79% of the randomized and treated patients were taking aspirin. Compared with placebo, clopidogrel 0.20 mg x kg(-1) x d(-1) resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. There was marked interpatient variability in the degree of platelet aggregation inhibition within each treatment-dose group and age group. No serious bleeding events occurred.

CONCLUSIONS: Clopidogrel 0.20 mg x kg(-1) x d(-1) in children 0 to 24 months of age achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Clopidogrel is well tolerated in infants and young children at this dose.

Rights and Permissions

Citation: Circulation. 2008 Jan 29;117(4):553-9. Epub 2008 Jan 14. doi 10.1161/CIRCULATIONAHA.107.715821

Related Resources

Link to article in PubMed

PubMed ID

18195173