A Phase 4 Randomized Clinical Trial of Andexanet Alfa [Andexanet Alfa for Injection] in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor
- Conditions
- Intracranial Hemorrhagebrain bleeding (e.g. subdural, subarachnoidal)
- Registration Number
- DRKS00017102
- Lead Sponsor
- Alexion Pharmaceutical, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 550
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 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.
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 [last dose 2.5 mg or greater], rivaroxaban [last dose 10 mg or greater], or edoxaban [last dose 30 mg or greater],
?= 15 hours prior to randomization.
?> 15 hours prior to randomization or unknown time of last dose, only if 1) the local anti-fXa activity > 100 ng/mL for direct fXa inhibitors (apixaban, rivaroxaban or edoxaban) as per standard of care, and 2) the local anti-fXa activity level is obtained within 2 hours prior to consent. Note: Patients enrolled in this manner should receive a high andexanet dosing regimen.
6. Time from bleeding symptom onset = 6 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. (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.)
7.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.
8.Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
9.NIHSS score = 35 at the time of consent.
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.
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.Purposefully left blank to align with the programmed database.
4.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).
5.Expected survival of less than 1 month (not related to the intracranial bleed).
6.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 (see Appendix H for DIC scoring algorithm).
7.Acute decompensated heart failure or cardiogenic shock at the time of randomization (see Appendix I for cardiogenic shock definition).
8.Severe sepsis or septic shock at the time of randomization (see Appendix I for sepsis definition).
9.The patient is a pregnant or lactating female.
10.Receipt of any of the following drugs or blood products within 7 days prior to consent:
a.VKA (e.g., warfarin).
b.Dabigatran.
c.PCC (e.g., KCentra®) or rfVIIa (e.g., NovoSeven®), or anti-inhibitor coagulant complex (e.g., FEIBA®), FFP, and whole blood.
11.Past use of andexanet (or planned use of commercial andexanet).
12.Treatment with an investigational drug < 30 days prior to consent.
13.Any tumor-related bleeding.
14.Known hypersensitivity to any component of andexanet.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Proportion of patients with good or excellent hemostatic efficacy as rated by an independent adjudication committee [Time frame 12 hours]
- Secondary Outcome Measures
Name Time Method Change from baseline in anti-fXa activity [Time frame: 1-3 hours]