A phase 4 Randomized Clinical Trial of Andexanet Alfa [Andexanet Alfa for injection] in acute intracranial haemorrhage in patients receiving an oral factor Xa inhibitor
- Conditions
- intracranial bleeding1000796310047075
- Registration Number
- NL-OMON49173
- Lead Sponsor
- Portola Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
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.
In the Netherlands, deferred consent procedure is allowed. 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 for 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,
ICH-GCP, the
Data Protection Directive (Directive 95/46/EC) and national and local
regulations.
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.
If a patient meets any of the following criteria, he/she is not eligible to
participate in this trial.
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:
a. Vitamin K Antagonist (VKA) (e.g., warfarin).
b. Dabigatran.
c. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoint<br /><br>• Effective hemostasis as determined by the blinded EAC.<br /><br><br /><br>Effective hemostasis is defined as no greater than a 35% increase from baseline<br /><br>in hematoma volume/thickness at 12 hours post randomization, AND less than a 7<br /><br>point increase from baseline NIHSS score at 12 hours post randomization </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Efficacy Endpoints<br /><br>• Maximum reduction in anti-fXa activity.<br /><br>• Minimum value of anti-fXa activity post randomization.</p><br>