A clinical trial to study the effect of andexanet alfa compared to the usual care with regards to stopping severe/life threatening bleeding in patients with bleeding inside the skull.
- Conditions
- Oral FXa inhibitor-treated patients with acute intracranial bleeding.MedDRA version: 20.0Level: LLTClassification code 10075279Term: Anticoagulant reversal therapySystem Organ Class: 100000004865Therapeutic area: Not possible to specify
- Registration Number
- EUCTR2018-002620-17-NL
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1200
1. Written informed consent. Either the patient or his or her legally
authorized representative (LAR) 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 (or LAR) will be obtained
as soon
as realistically possible after inclusion in the study 18-513 and in
accordance with
the Declaration of Helsinki, International Council for Harmonization of
Technical Requirements for Pharmaceuticals for Human Use (ICH), Good
Clinical Practice (GCP), the EU General Data Protection Regulation (GDPR) and national and local regulations.
2. Age =18 years old at the time of consent.
3. An acute intracranial bleeding episode, defined as an estimated blood
volume =0.5 mL to =60 mL acutely observed radiographically within the
cranium. Patients may have extracerebral (e.g., subdural, subarachnoid,
epidural) or extracranial bleeding (e.g., gastrointestinal, intraspinal)
additionally, but the intracebral hemorrhage must be considered the
significant bleed at the time of enrollment.
4. 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).
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, if
1) the local anti-fXa activity > 100 ng/mL (for direct fXa inhibitors (apixaban, rivaroxaban or edoxaban) and
2) the local anti-fXa activity level is obtained within 2 hours prior to consent, performed as per standard of care.
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 repeated 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
women of childbearing potential).
9. NIHSS score = 35 at the time of consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1010
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 and that are
not expected to significantly affect haematoma volume are allowed (e.g.,
Burr holes for intracranial pressure monitoring, endoscopy,
bronchoscopy, central lines—see Section 7.2 and 7.3 and Appendix G).
2. Glasgow Coma score (GCS) < 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 nonneurologic
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 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, pulmonary embolism [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 A for cardiogenic shock definition).
8. Severe sepsis or septic shock at the time of randomization (see
Appendix A 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. 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®), 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method