High-dose versus low-dose tranexamic acid for paediatric craniosynostosis surgery: a double-blind randomised controlled non-inferiority trial.

BACKGROUND

Tranexamic acid (TXA) reduces blood loss and transfusion in paediatric craniosynostosis surgery. The hypothesis is that low-dose TXA, determined by pharmacokinetic modelling, is non-inferior to high-dose TXA in decreasing blood loss and transfusion in children.

METHODS

Children undergoing craniosynostosis surgery were enrolled in a two-centre, prospective, double-blind, randomised, non-inferiority controlled trial to receive high TXA (50 mg kg followed by 5 mg kg h) or low TXA (10 mg kg followed by 5 mg kg h). Primary outcome was blood loss. Low dose was determined to be non-inferior to high dose if the 95% confidence interval (CI) for the mean difference in blood loss was above the non-inferiority margin of -20 ml kg. Secondary outcomes were transfusion, TXA plasma concentrations, and biological markers of fibrinolysis and inflammation.

RESULTS

Sixty-eight children were included. Values were non-inferior regarding blood loss (39.4 [4.4] vs 40.3 [6.2] ml kg [difference=0.9; 95% CI: -14.2, 15.9]) and blood transfusion (21.3 [1.6] vs 23.6 [1.5] ml kg [difference=2.3; 95% CI: -2.1, 6.7]) between high-dose (n=32) and low-dose (n=34) groups, respectively. The TXA plasma concentrations during surgery averaged 50.2 (8.0) and 29.6 (7.6) μg ml. There was no difference in fibrinolytic and inflammatory biological marker concentrations. No adverse events were observed.

CONCLUSIONS

Tranexamic acid 10 mg kg followed by 5 mg kg h is not less effective than a higher dose of 50 mg kg and 5 mg kg h in reducing blood loss and transfusion in paediatric craniosynostosis surgery.

CLINICAL TRIAL REGISTRATION

NCT02188576.