Trial of Andexanet in ICH Patients Receiving an Oral FXa Inhibitor
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Randomized, controlled clinical trial evaluating the efficacy and safety of andexanet versus usual standard of care in patients with intracranial hemorrhage anticoagulated with a direct oral anticoagulant
Condition or disease
Acute Intracranial Hemorrhage
Drug: andexanet alfa
This is a randomized, multicenter clinical trial designed to determine the efficacy and safety of andexanet compared to usual care in patients presenting with acute intracranial hemorrhage within 12 hours of symptom onset and within 15 hours of taking an oral factor Xa inhibitor. The study will use a prospective, randomized, open label (PROBE) design. The primary efficacy outcome will be adjudicated by a blinded Endpoint Adjudication Committee. To support the adjudication of hemostatic efficacy, a blinded Imaging Core Laboratory will review all available scans. Approximately 440 patients are planned to be enrolled in the study.
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Layout table for eligibility information
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Written informed consent. 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.
Age 18 years old or greater at the time of consent.
An acute intracranial bleeding episode, defined as any amount of blood acutely observed radiographically within the cranium. Patients may have extracranial bleeding (e.g., gastrointestinal, intraspinal) additionally, but the intracranial hemorrhage must be considered the primary bleed.
Performance of a head CT or MRI scan demonstrating the intracranial bleeding within 2 hours prior to randomization (the baseline scan may be repeated to meet this criterion).
Treatment with an oral FXa inhibitor (apixaban, rivaroxaban, or edoxaban) within 15 hours prior to randomization. If the time of last dose is unknown, the patient is not eligible for the study. If a patient is documented to have an anti-fXa activity > 100 ng/mL within 2 hours prior to consent, they may be enrolled irrespective of the time since last dose (as long as it is known).
Time from bleeding symptom onset < 12 hours prior to the baseline imaging scan. Time of trauma (if applicable) or time last seen normal may be used as surrogates for time of symptom onset.
Planned surgery, including Burr holes for hematoma drainage, within 12 hours after randomization. Minimally invasive surgery/procedures not directly related to the treatment of intracranial bleeding are allowed (e.g., Burr holes for intracranial pressure monitoring, endoscopy, bronchoscopy, central lines—see Section 7.3 and Appendix F).
Glasgow Coma score < 7 at the time of consent. If a patient is intubated and/or sedated at the time of consent, they may be enrolled if it can be documented that they were intubated/sedated for non-neurologic reasons within 2 hours prior to consent.
Estimated intracerebral hematoma volume > 60 mL assessed by the baseline CT or MRI.
Any bleeding into the (intracranial) epidural space.
Anticipation that the baseline and follow up brain scans will not be able to use the same imaging modalities (i.e., patients with a baseline CT scan should have a CT scan in follow up; similarly for MRI).
Expected survival of less than 1 month.
Recent history (within 2 weeks) of a diagnosed Thrombotic Event (TE) or clinically relevant symptoms of the following: Venous Thromboembolism (VTE: e.g., deep venous thrombosis, pulmonary embolism, cerebral venous thrombosis), myocardial infarction, Disseminated Intravascular Coagulation (DIC), cerebral vascular accident, transient ischemic attack, acute coronary syndrome, or arterial systemic embolism within 2 weeks prior to Screening (see Appendix G for DIC scoring algorithm).
Acute decompensated heart failure or cardiogenic shock at the time of randomization (see Appendix H for cardiogenic shock definition).
Severe sepsis or septic shock at the time of randomization (see Appendix H for sepsis definition).
Pregnant or lactating.
Receipt of any of the following drugs or blood products within 7 days prior to consent:
Vitamin K Antagonist (VKA) (e.g., warfarin).
Prothrombin Complex Concentrate products (PCC, e.g., Kcentra®) or recombinant factor VIIa (rfVIIa) (e.g., NovoSeven®), or anti-inhibitor coagulant complex (e.g., FEIBA®).
Past or planned use of andexanet.
Treatment with an investigational drug < 30 days prior to consent.