The "OPTI-CLOT" trial. A randomised controlled trial on periOperative PharmacokineTIc-guided dosing of CLOTting factor concentrate in haemophilia A

Abstract

Haemophilia A is an X-linked inherited, rare bleeding disorder, caused by a deficiency of coagulation factor VIII (FVIII). Previous studies in prophylactic dosing have demonstrated that FVIII consumption can be significantly reduced by individualising dosing based on combined analysis of individual pharmacokinetic (PK) profiling and population PK data (Bayesian analysis). So far, no studies have been performed that address perioperative concentrate consumption using iterative PK-guided dosing based on a PK population model. The "OPTI-CLOT" trial is an open-label, prospective, multicentre randomised controlled superiority trial (RCT), aiming to detect a 25 % difference in perioperative FVIII concentrate consumption with iterative Bayesian PK-guided dosing in comparison to the standard dosing procedure. Sixty haemophilia A patients ≥ 12 years of age, with FVIII plasma levels ≤ 0.05 IUml(-1) will be included requiring FVIII replacement therapy administered either by continuous or bolus infusion for an elective, low or medium risk surgical procedure. The proposed study aims to investigate a novel perioperative iterative PK-guided dosing strategy, based on a recently constructed perioperative PK population model. This model will potentially decrease underdosing and overdosing of clotting factor concentrate and is expected to overall reduce FVIII consumption by minimally 25 %. Moreover, participating hospitals will gain experience with PK-guided dosing, facilitating future implementation of this intervention which is expected to optimise current care and reduce costs of treatment.

Keywords: Bayesian analysis; Haemophilia therapy; factor VIII; factor concentrates; pharmacokinetics.