Oral FXa inhibitor-treated patients who require urgent surgery. MedDRA version: 20.0 Level: LLT Classification code 10075279 Term: Anticoagulant reversal therapy System Organ Class: 100000004865
Conditions
Sponsors
Alexion Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All of the following criteria must be met for the patient to be eligible: 1. Either the patient or their medical proxy (or legal designee) has given written informed consent. 2. Age = 18 and 15 hours prior to start of surgery or unknown time from the last dose, if documented anti fXa activity is > 100 ng/mL (> 0.5 IU/mL for enoxaparin, or over the equivalent IU/mL threshold on a low molecular weight heparin assay; see Laboratory Manual) within 2 hours prior to consent. Note: Patients enrolled in this manner should receive a highandexanet dosing regimen. 5. Have a negative pregnancy test documented prior to enrollment (for women of childbearing potential). 6. Willingness to use highly effective methods of contraception through 30 days following study drug dose (for female and male patients who are fertile). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: If a patient meets any of the following criteria, he or she is not eligible: 1. Surgery for which the risk of clinically meaningful uncontrolled or unmanageable bleeding is low. 2. Acute life-threatening bleeding (ISTH criteria) at the time of Screening: a. The patient has acute-overt bleeding that is potentially life threatening, e.g., with signs or symptoms of hemodynamic compromise, such as severe hypotension, poor skin perfusion, mental confusion, low urine output that cannot be otherwise explained. b. The patient has overt bleeding associated with a fall in hemoglobin level by =2g/dL, OR, a hemoglobin =8 g/dL if no baseline hemoglobin is available. c. The patient has acute bleeding in a critical area or organ, such as pericardial, intracranial, or intraspinal. 3. Any surgical procedure requiring cardiopulmonary bypass, an intraaortic catheter, or the intraoperative use of systemic, intravascular, unfractionated heparin. 4. Primary procedure for efficacy assessment is a non-surgical interventional procedure (e.g, lumbar puncture, skin biopsy, cardiac catheterization, endoscopic retrograde cholangio-pancreatography). 5. Expected survival of < 1 month due to comorbidity. 6. Known "Do Not Resuscitate" order or similar advanced directive. 7. The patient has a recent history (within 30 days prior to screening) of a diagnosed TE as follows: venous thromboembolism (including deep vein thrombosis, pulmonary embolism, intracardiac thrombus), myocardial infarction (including asymptomatic troponin elevations), disseminated intravascular coagulation, acute traumatic coagulopathy, cerebrovascular accident, transient ischemic attack, unstable angina pectoris hospitalization, or severe peripheral vascular disease. 8. Acute decompensated heart failure or cardiogenic shock at the time of screening. 9. The patient has severe sepsis or septic or severe hemorrhagic shock at the time of Screening. 10. The patient has heparin-induced thrombocytopenia (with or without thrombosis). 11. Inherited coagulopathy (e.g., anti-phospholipid antibody syndrome, protein C/S deficiency, Factor V Leiden) at the time of Screening. 12. Platelet count < 80,000/µL at the time of Screening. 13. Last dose of apixaban < 2.5 mg, rivaroxaban < 10 mg, edoxaban < 30 mg, or enoxaparin 40 mg. 14. The patient is pregnant or a lactating female. 15. The patient has received any of the following drugs or blood products within 7 days of enrollment: o Vitamin K antagonists (e.g., warfarin). o Dabigatran. o Prothrombin complex concentrate products (e.g., Kcentra®) or recombinant factor VIIa (e.g., NovoSeven®). o Whole blood, plasma fractions. Note: Administration of tranexamic acid, platelets or packed red blood cells is not an exclusion criterion. 16. The patient was treated with an investigational drug < 30 days prior to Screening. 17. Prior treatment with andexanet. 18. Known hypersensitivity to any component of andexanet. 19. Known allergic reaction to hamster proteins. 20. Known or suspected (i.e., presumed positive) COVID-19-related illness at the time of Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the hemostatic efficacy following andexanet treatment.;Secondary Objective: • To evaluate the effect of andexanet on anti-fXa activity. ;Primary end point(s): The primary efficacy endpoint is the achievement of effective hemostasis, as determined by the surgeon’s assessment of intraoperative hemostasis and confirmed by adjudication by an independent EAC.;Timepoint(s) of evaluation of this end point: From start of surgery to the end of the procedure | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoint is the percent change in anti-fXa activity from baseline to the evaluation period nadir. ;Timepoint(s) of evaluation of this end point: The evaluation period starts 5 minutes after the end of the andexanet bolus and ends just prior to the end of the andexanet infusion | — |
Countries
Austria, France, Germany, Israel, Japan, United States
Contacts
Public ContactEuropean Clinical Trial Information
Alexion Europe SAS
Outcome results
None listed