Prospective, Open-label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor who Require Urgent Surgery (ANNEXA-S)
- Conditions
- Bleedingurgent surgery
- Registration Number
- DRKS00021080
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting stopped after recruiting started
- Sex
- All
- Target Recruitment
- 10
1.Either the patient or their medical proxy (or legal designee) has given written informed consent.
2. Age = 18 and < 85 years old.
3. Requires urgent surgical intervention that must occur within 12 hours of consent, for which reversal of anti-fXa activity is judged necessary.
4. Received 1 of the following FXa inhibitors apixaban, rivaroxaban, edoxaban, or enoxaparin (dose of enoxaparin = 1 mg/kg/d) within 15 hours prior to start of surgery. If the time from the last dose is unknown or greater than 15 hours, the patient may be enrolled provided a local laboratory anti-fXa activity level obtained within 2 hours prior to consent is >100 ng/mL (>0.5 IU/mL for enoxaparin).
5. Have a negative pregnancy test documented prior to enrollment (for women of childbearing potential).
6. Willingness to use medically acceptable methods of contraception through 30 days following study drug dose (for female and mal patients who are fertile)
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 intra-aortic 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)
12. Last dose of apixaban < 2.5 mg, rivaroxaban < 10 mg, edoxaban < 30 mg, or enoxaparin 40 mg.
13. The patient is pregnant or a lactating female.
14. 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.
15. The patient was treated with an investigational drug < 30 days prior to Screening.
16. Prior treatment with andexanet.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate hemostatic efficacy following andexanet alfa (andexanet) treatment.<br><br>The evaluation period is 5 min after the end of bolus administration until immediately before the end of the andexanet infusion, which is also the end of surgery. <br><br>The operating surgeon must assess both baseline and haemostatic efficacy intra-operatively, the latter according to Table 3 of the protocol.<br><br>Confirmation by an independent expert panel is also part of the assessment.
- Secondary Outcome Measures
Name Time Method To evaluate the effect of andexanet on anti-fXa activity.