Preliminary results of the PICOLO study of clopidogrel use in children have been published early online in Circulation.
The appropriate dose of clopidogrel in children has yet to be established, and in this pharmacodynamic study the authors sought to determine the dose that would achieve inhibition of platelet aggregation similar to that achieved for the 75mg dose in adults (ie a mean of 30-50% inhibition of 5micromol/l ADP-induced platelet aggregation).
A secondary objective was to assess clopidogrel’s safety and tolerability in this population.
A total of 86 participants were randomised and treated in the study (73 completed the study); all were under 24 months old with congenital heart disease (systemic-to-pulmonary artery shunt) or another cardiac condition with a risk of arterial thrombosis (eg Kawasaki disease or intravascular or intracardiac stent).
Exclusion criteria included weight of below 2kg, being of <35 weeks gestation, any ongoing risk of bleeding (eg haemophilia) and planned or current use of anticoagulants (aspirin was permitted and taken by 79% of those treated).
Patients were randomised to clopidogrel (0.01, 0.10, 0.20 and 0.15 mg/kg daily) or placebo for 7-28 days; platelet aggregation was assessed at baseline and steady-state.
The investigators found clopidogrel at a dose of 0.2mg/kg/day achieves a platelet inhibition level similar to that in adults taking 75mg/d, with a mean 49.3% (95% CI 25.7-72.8%) inhibition of the maximum extent of platelet aggregation compared to placebo.
No serious haemorrhagic events were noted during the study; two in the clopidogrel group and two in the placebo group experienced minor bleeding.
Only one event – a decreased platelet count – was considered to be possibly related to treatment.
The authors note that the 0.2mg/kg/day dose is considerably lower per kilogram of bodyweight than that for adults; previous reports of clopidogrel use in paediatric patients have involved much higher doses and have not been as well tolerated.
They caution that their results are restricted to the particular study population and should not be assumed to be generalisable to all children with thrombotic disease.
They briefly mention the upcoming Clopidogrel to Lower Arterial thrombotic Risk In NEonates and infants Trial (CLARINET), which will assess efficacy and safety of clopidogrel 0.2mg/kg/day in neonates and infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary artery shunt.