Abstract Number: PB0896
Meeting: ISTH 2020 Congress
Background: Pharmacokinetic (PK)-guided dosing of factor VIII (FVIII) concentrates is an important tool for hemophilia A patients undergoing surgery to prevent underdosing with increased risk of surgical bleeding as well as overdosing associated with unnecessary treatment costs and risk of trombosis. Despite the fact that several PK studies have been performed, no randomized controlled trial has been performed which compares perioperative PK-guided dosing with routine dosing based on bodyweight.
Aims: Compare PK-guided iterative dosing versus standard FVIII replacement therapy in perioperative hemophilia A patients to establish effect on FVIII concentrate consumption.
Methods: In a multicenter, open-label, randomized controlled trial, hemophilia A patients (FVIII< 0.05 IU/mL) were randomly assigned to treatment arms in 1:1 ratio, stratified for mode of administration and severity of surgical procedure. Primary endpoint was FVIII concentrate consumption during total perioperative period (linear regression). Secondary endpoints included: efficacy of FVIII range targeting (linear mixed effects modeling), safety e.g. bleeding (Chi-square test), and duration of hospitalization (linear regression). The study was approved by Medical Ethical Committees. All patients gave written informed consent.
Results: Sixty-five severe or moderately affected hemophilia A patients have been included. Total perioperative FVIII consumption was similar between PK-guided (mean: 329±199 IU/kg) and standard treatment arm (mean: 375±205 IU/kg) (P = 0.83, Table 1). However, PK-guided dosing significantly improved FVIII range targeting (Figure 1). The relative quadratic difference in the ratio between FVIII-measured and FVIII-target was 0.186 (95% CI 0.119 – 0.290) adjusted for blood type, age, weight, severity of surgery, mode of infusion, perioperative time point. Both perioperative bleeding events and hospitalization period did not differ between treatment arms.
Conclusions: This first RCT shows that PK-guided iterative dosing does not decrease perioperative FVIII concentrate consumption in hemophilia A patients. However, PK-guided dosing leads to more optimal targeting of pre-specified FVIII levels and more precise perioperative dosing.
|Regression Coefficient (B)||Standard Error||95% Confidence interval||P value|
|Randomization result (PK-guided dosing)||-10||49||-108||88||0.834|
|Blood type (Blood type O)||50||49||-48||149||0.309|
|Planned type of FVIII administration (continuous infusion)||118||60||-3||239||0.055|
|Planned type of surgical procedure (medium risk)||105||62||-20||230||0.099|
[Table 1. Multivariate linear regression model of FVIII concentrate consumption (IU/kg) in perioperative hemophilia A (FVIII<0.05 IU/ml) patients.]
To cite this abstract in AMA style:van Moort I, Preijers T, Bukkems L, Hazendonk H, Laros-van Gorkom B, Beckers E, Nieuwenhuizen L, van der Meer F, Ypma P, Coppens M, Fijnvandraat K, Schutgens R, Meijer K, Leebeek F, Mathot R, Cnossen M, OPTI-CLOT Study Group . A Randomized Controlled Trial: Pharmacokinetic-Guided Dosing of Factor VIII Concentrate Versus Standard Replacement Therapy in Perioperative Hemophilia A Patients (OPTI-CLOT Trial) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/a-randomized-controlled-trial-pharmacokinetic-guided-dosing-of-factor-viii-concentrate-versus-standard-replacement-therapy-in-perioperative-hemophilia-a-patients-opti-clot-trial/. Accessed May 6, 2021.
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