Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor Who Have Acute Major Bleeding

Annexa-4 [NCT02329327]

Description:  The purpose of this study is to evaluate the hemostatic efficacy of andexanet alfa in patients receiving a factor Xa inhibitor who are experiencing an acute major bleed. The safety of andexanet will also be studied.

Drug: Recombinant Factor Xa Inhibitor Antidote

Primary Investigator: Kereiakes

Drug/Device Information
Study of Andexanet Alfa in patients receiving a Factor Xa Inhibitor who have acute major bleeding
Andexanet has been specifically designed to neutralize the anticoagulant effect of direct and indirect fXa inhibitors
Andexanet is a modified fXa protein that has been truncated and inactivated so that it lacks physiologic blood coagulation factor activity but retains its high affinity for fXa inhibitors
Open-Label study
Portola Pharmaceuticals, Inc.
Major Inclusion and Exclusion
The patient must have an acute overt major bleeding episode requiring urgent reversal of anticoagulation defined by 1,2 or 3
1. Acute overt bleeding that is potentially life-threatening, e.g., with signs or symptoms of hemodynamic compromise
2. Acute overt bleeding associated with a fall in hemoglobin level by ≥ 2 g/dL
2. Cont. OR a Hb ≤ 8 g/dL if no baseline Hb is available
2. Cont. OR, in the opinion of the investigator that the patient’s hemoglobin will fall to ≤ 8 g/dL with resuscitation
3. Acute symptomatic bleeding in a critical area or organ, such as, retroperitoneal, intra-articular or pericardial, intracranial or intramuscular with compartment syndrome
Received one of the following within 18 hours prior to andexanet administration: apixaban, rivaroxaban, edoxaban or enoxaparin (dose of enoxaparin ≥ 1mg/kg/d)
Not scheduled to undergo surgery in less than 12 hours with the exception of minimally invasive surgery/procedures
No Glasgow coma score < 7
No estimated intracerebral hematoma volume >60 cc
No diagnosed thrombotic event -MI, DIC, CVA, TIA, unstable angina pectoris hospitalization, or severe PVD within 2 weeks
No Vitamin K antagonist; Dabigatran; Prothrombin Complex Concentrate products (PCC, e.g., Kcentra) or recombinant factor VIIa (rfVIIa) (e.g., NovoSeven); Whole blood plasma fractions within 7 days