Eligibility Details:
Inclusion Criteria:
1. 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.
2. Age 18 years old or greater at the time of consent.
3. 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.
4. 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).
5. 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).
6. 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.
Exclusion Criteria:
1. 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).
2. 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.
3. Estimated intracerebral hematoma volume > 60 mL assessed by the baseline CT or MRI.
4. Any bleeding into the (intracranial) epidural space.
5. 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).
6. Expected survival of less than 1 month.
7. 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).
8. Acute decompensated heart failure or cardiogenic shock at the time of randomization
(see Appendix H for cardiogenic shock definition).
9. Severe sepsis or septic shock at the time of randomization (see Appendix H for sepsis
definition).
10. Pregnant or lactating.
11. Receipt of any of the following drugs or blood products within 7 days prior to
consent:
1. Vitamin K Antagonist (VKA) (e.g., warfarin).
2. Dabigatran.
3. Prothrombin Complex Concentrate products (PCC, e.g., Kcentra®) or recombinant
factor VIIa (rfVIIa) (e.g., NovoSeven®), or anti-inhibitor coagulant complex
(e.g., FEIBA®).
12. Past or planned use of andexanet.
13. Treatment with an investigational drug < 30 days prior to consent.
common.study.methods.has-drugs-yes
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