A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor

  • STATUS
    Recruiting
  • End date
    Jul 30, 2024
  • participants needed
    1200
  • sponsor
    Alexion Pharmaceuticals
Updated on 25 October 2022
Investigator
Alexion Pharmaceuticals, Inc.
Primary Contact
Clinical Trial Site (1.7 mi away) Contact
+179 other location

Summary

Randomized, controlled clinical trial evaluating the efficacy and safety of andexanet alfa versus usual care in patients with intracranial hemorrhage anticoagulated with a direct oral or indirect subcutaneous/intravenous anticoagulant

Description

This is a randomized, multicenter clinical trial designed to determine the efficacy and safety of andexanet alfa compared to usual care in patients presenting with acute intracranial hemorrhage within 6 hours of symptom onset to baseline scan 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. Between 900 and 1200 patients are planned to be enrolled in the study.

Details
Condition Acute Intracranial Hemorrhage
Treatment Placebo, Usual Care, Andexanet alfa
Clinical Study IdentifierNCT03661528
SponsorAlexion Pharmaceuticals
Last Modified on25 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent. Either the patient or his or her medical proxy (or legally authorized representative if permissible by local or regional laws and regulations) has been adequately informed of the nature and risks of the study and has given written informed consent prior to Screening
Deferred consent procedure is allowed where approved by local ethics committees. In cases of deferred consent, the time of the study physician's documented decision to include the patient into the study will serve as "time of consent" with respect to protocol-specific procedures
In all cases where the patient does not sign informed consent prior to study entry, informed consent from the patient will be obtained as soon as realistically possible after inclusion in the trial and in accordance with the Declaration of Helsinki, International Conference on Harmonization-Good Clinical Practice (GCP), the Data Protection Directive (Directive 95/46/EC) and national and local regulations
Age ≥ 18 years old at the time of consent
An acute intracerebral bleeding episode, defined as an estimated blood volume ≥ 0.5 to ≤ 60 mL acutely observed radiographically within the cerebrum. Patients may have extracerebral (e.g., subdural, subarachnoid, epidural) or extracranial (e.g., gastrointestinal, intraspinal) bleeding additionally, but the intracerebral hemorrhage must be considered the most clinically significant bleed at the time of enrollment
Performance of a head CT or MRI scan demonstrating the intracerebral bleeding within 2 hours prior to randomization (the baseline scan may be repeated only once to meet this criterion)
Treatment with an oral FXa inhibitor (apixaban [last dose 2.5 mg or greater], rivaroxaban [last dose 10 mg or greater], edoxaban [last dose 30 mg or greater], or enoxaparin [last dose 1 mg or greater])
≤ 15 hours prior to randomization
> 15 hours prior to randomization or unknown time of last dose, if documented anti fXa activity is > 100 ng/mL for direct fXa inhibitors (apixaban, rivaroxaban or edoxaban) or > 0.5 IU/mL for enoxaparin may be enrolled, irrespective of the time of the last dose, and the patient is within 2 hours prior to consent. Note: Patients enrolled in this manner should receive a high andexanet dosing regimen
Time from bleeding symptom onset < 6 hours prior to the baseline imaging scan. Time of
Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified guidance for avoiding pregnancy for 30 days after the last dose of study drug
trauma (if applicable) or time last seen normal may be used as surrogates for
Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential)
time of symptom onset. (If the baseline scan is repeated to meet Inclusion
Criterion #4, the time from bleeding symptom onset must be < 6 hours prior to
the repeat baseline imaging scan.)

Exclusion Criteria

Expected survival of less than 1 month (not related to the intracranial bleed)
Purposefully left blank
If a patient meets any of the following criteria, he or she is not eligible to participate
in this trial
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 and that are not expected to significantly affect
hematoma volume are allowed (e.g., Burr holes for intracranial pressure monitoring
endoscopy, bronchoscopy, central lines
consent
GCS 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
Dabigatran
intubated/sedated for non-neurologic reasons within 2 hours prior to consent
Past use of andexanet (or planned use of commercial andexanet)
Anticipation that the baseline and follow up brain scans will not be able to use the
Treatment with an investigational drug < 30 days prior to consent
same imaging modalities (i.e., patients with a baseline CT scan should have a CT scan
Any tumor-related bleeding
in follow up; similarly, for MRI)
Known hypersensitivity to any component of andexanet
VKA (e.g., warfarin)
Recent history (within 2 weeks) of a diagnosed TE or clinically relevant symptoms of
the following
○ Venous Thromboembolism (VTE: e.g., deep venous thrombosis, PE, cerebral venous
thrombosis), myocardial infarction (MI), Disseminated Intravascular Coagulation (DIC)
cerebral vascular accident, transient ischemic attack (TIA), acute coronary syndrome
or arterial systemic embolism
Acute decompensated heart failure or cardiogenic shock at the time of randomization
Severe sepsis or septic shock at the time of randomization
The patient is a pregnant or lactating female
Receipt of any of the following drugs or blood products within 7 days prior to
PCC (e.g., KCentra®) or rfVIIa (e.g., NovoSeven®), or anti-inhibitor coagulant
complex (e.g., FEIBA®), FFP, and whole blood
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