Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial
Authors
Li, Jennifer S.Yow, Eric
Berezny, Katherine Y.
Bokesch, Paula M.
Talajasjo, Matsato
Graham, Thomas P. Jr.
Sanders, Stephen P.
Sidi, Daniel
Bonnet, Damien
Ewert, Peter
Jennings, Lisa K.
Michelson, Alan D.
UMass Chan Affiliations
Department of PediatricsDocument Type
Journal ArticlePublication Date
2008-01-29Keywords
AspirinDose-Response Relationship, Drug
Hemorrhage
Humans
Infant
Infant, Newborn
Platelet Aggregation
Platelet Aggregation Inhibitors
Ticlopidine
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
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.Source
Circulation. 2008 Jan 29;117(4):553-9. Epub 2008 Jan 14. doi 10.1161/CIRCULATIONAHA.107.715821DOI
10.1161/CIRCULATIONAHA.107.715821Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43299PubMed ID
18195173Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1161/CIRCULATIONAHA.107.715821