Abstract 17765: A Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Healthy Male Volunteers

INTRODUCTION: The new oral anticoagulants are effective alternatives for warfarin but specific antidotes are not yet available for these agents to manage life-threatening bleeding or when emergency surgery is necessary. A specific antibody fragment (Fab) is being developed which binds dabigatran with high affinity and thereby prevents dabigatran inhibition of thrombin. For the first time in human volunteers, we determined whether equimolar doses of Fab would reverse the anticoagulant effects of dabigatran. METHODS: Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the Fab were investigated in a randomized, double-blind, placebo controlled study in 145 healthy male volunteers. In part I of the study, subjects received single rising i.v. doses of up to 8 g Fab. In part II, Fab doses of 1 g, 2 g and 4 g were administered as 5 min i.v. infusion in the presence of dabigatran (220 mg bid for 4 days). Concentrations of unbound dabigatran were determined as a measure of pharmacologically ac...