Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor XA Inhibitor Who Have Acute Major Bleeding (Annexa-4), Amendment 6
- Conditions
- Acute Major Bleeding
- Registration Number
- DRKS00012316
- Lead Sponsor
- Portola Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 479
1. Either the patient or his or her medical proxy (or legally acceptable designee) has been
adequately informed of the nature and risks of the study and has given written informed
consent prior to Screening.
2. The patient must be at least 18 years old at the time of Screening.
3. The patient must have an acute overt major bleeding episode requiring urgent reversal of
anticoagulation. Acute major bleeding requiring urgent reversal of anticoagulation is
defined by at least ONE of the following:
• 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.
• Acute overt bleeding associated with a fall in hemoglobin level by = 2 g/dL, OR
a Hgb = 8 g/dL if no baseline Hgb is available.
• Acute bleeding in a critical area or organ, such as intraspinal, pericardial, or intracranial
4. The patient, for whom the bleeding is intracranial or intraspinal must have undergone a CT
or MRI scan demonstrating the bleeding.
5. The patient received or is believed to have received one of the following within 18 hours
prior to andexanet administration: apixaban, rivaroxaban, edoxaban, or enoxaparin (dose of
enoxaparin = 1 mg/kg/d).
6. For patients with ICH, there must be a reasonable expectation that andexanet treatment will commence within 2 hours of the baseline imaging evaluation.
1) Patients are excluded if they are scheduled to undergo surgery in less than 12 hours, with the
exception of minimally invasive surgery/procedures (e.g., endoscopy, bronchoscopy, central
lines, Burr holes - see more examples in Appendix G).
2) A patient with ICH has any of the following:
• Glasgow Coma Score < 7
• Estimated intracerebral hematoma volume > 60 cc as assessed by the CT or MRI
3) Patients with visible, musculoskeletal, or intra-articular bleeding as their qualifying bleed.
4) The patient has an expected survival of less than 1 month.
5) The patient has a recent history (within 2 weeks) of a diagnosed thrombotic event (TE)
as follows: venous thromboembolism (VTE; e.g., deep vein thrombosis, pulmonary
embolism, intracranial venous thrombosis), myocardial infarction, disseminated
intravascular coagulation (DIC), cerebral vascular accident, transient ischemic attack,
unstable angina pectoris hospitalization, or severe peripheral vascular disease within
2 weeks prior to screening (see Appendix E for DIC scoring algorithm).
6) The patient has severe sepsis or septic shock at the time of Screening (see definition
Appendix F).
7) The patient is pregnant or a lactating female.
8) The patient has received any of the following drugs or blood products within 7 days or
Screening:
• Vitamin K antagonist (VKA) (e.g., warfarin).
• Dabigatran.
• Prothrombin Complex Concentrate products (PCC, e.g., Kcentra®) or recombinant
factor VIIa (rfVIIa) (e.g., NovoSeven®).
• Whole blood, plasma fractions. Note: Administration of platelets or packed red blood
cells (PRBCs) is not an exclusion criterion.
9) The patient was treated with an investigational drug < 30 days prior to Screening.
10) Planned administration of PCC, fresh frozen plasma (FFP), or rfVIIa from Screening until
within 12 hours after the end of the andexanet infusion.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objectives of the study are to demonstrate the decrease in anti-fXa activity following andexanet treatment and to evaluate the hemostatic efficacy of andexanet in patients receiving a fXa inhibitor who have acute major bleeding and reduced fXa activity.<br><br>Hemostatic efficacy wil be evaluated by the Adjudication Committee based on clinical data (symptoms, physical exam, blood tests, imaging tests, etc.) collected over the first 12 hours following the end of andexanet treatment on Day 1.<br><br>The change from baseline in anti-fXa activity will be based on two blood tests obtained at the end of the andexanet bolus administration and at the end of the andexanet continuous infusion.
- Secondary Outcome Measures
Name Time Method To assess the relationship between decrease in anti-fXa activity and achievement of hemostatic efficacy in patients receiving a fXa inhibitor who have acute major bleeding and reduced fXa activity.