Andexanet Alfa for the treatment of brain hemorrhages in patients taking anticoagulant medications.
Zusammenfassung der Studie
A brain hemorrhage, especially in patients who have regularly taken an anticoagulant medication prior to the hemorrhage, can lead to permanent damage to the brain. There is a risk that the bleeding will continue to increase, which can lead to worsening disability or death. At this time, there is no treatment that has been proven to stop a brain hemorrhage and improve symptoms in patients who regularly take one of the anticoagulant medications and suffer a brain hemorrhage. In this clinical study, we are testing the efficacy and safety of the drug "Andexanet Alfa," which can block the anticoagulant effect of factor Xa inhibitors. We want to find out how well Andexanet, compared to the usual standard treatment, reverses the effect of anticoagulant medications in patients who experience a brain hemorrhage within 15 hours of taking one of the above-mentioned anticoagulant medications. Furthermore, we want to investigate how well Andexanet helps, compared to the usual treatment, to stop brain bleeding. This is a randomized study, meaning that study participants are randomly assigned to either the study treatment or the standard treatment (50% in each group). This approach is necessary to clearly demonstrate the effect of Andexanet Alfa. The study duration for patients is approximately 37 days. Between 900 and 1200 patients worldwide will participate in the study. Andexanet has recently been approved in both the USA and Europe with an accelerated/conditional approval, meaning it can be prescribed by a doctor even though the benefits of the drug have not yet been definitively proven. In Switzerland, the drug is approved.
(BASEC)
Untersuchte Intervention
Patients receive one of two dosing options of Andexanet Alfa. The assignment to one of the two groups depends on which anticoagulant medication the patients have taken in what dosage just before the brain hemorrhage, and when the last medication was taken before the brain hemorrhage occurred. 400 mg (low dose) or 800 mg (high dose) of Andexanet Alfa are administered intravenously as a rapid injection over a period of 30 minutes.
This is followed by a continuous infusion of approximately 2 hours. Depending on which study medication group the patients belong to, they receive either 480 mg (low dose) or 960 mg (high dose) of Andexanet Alfa administered intravenously. A transition between treatment groups is not possible. The usual standard care consists of any other treatments than Andexanet Alfa that the investigator and/or treating physicians deem appropriate.
(BASEC)
Untersuchte Krankheit(en)
Patients taking an anticoagulant medication and suffering a brain hemorrhage.
(BASEC)
• Acute brain hemorrhages that occurred within the last 6 hours; • Patients are being treated with a new oral anticoagulant (Apixaban, Rivaroxaban, Edoxaban, Enoxaparin), which was last taken within 15 hours; • The time since the onset of bleeding symptoms is a maximum of 6 hours; • Confirmation of the brain hemorrhage by medical imaging (CT or MRI) within 2 hours prior to inclusion in the study. • Follow the protocol instructions to avoid pregnancy for 30 days after the last dose of the study medication. (BASEC)
Ausschlusskriterien
• A Glasgow Coma Score of less than 7 at the time of registration. This Glasgow Coma Score, GCS, is an assessment of consciousness and brain function after a head injury; • The estimated extent of the brain hemorrhage is between 0.5 ml and 60 ml. • The presence of a thrombotic event within the last two weeks. A thrombosis is the blockage of a blood vessel by a blood clot; • Anticoagulant treatment within 7 days after the informed consent. (BASEC)
Studienstandort
Basel, Bern, Zürich
(BASEC)
Sponsor
nicht verfügbar
Kontakt für weitere Auskünfte zur Studie
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
21.09.2020
(BASEC)
ICTRP Studien-ID
NCT03661528 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
nicht verfügbar
Wissenschaftlicher Titel
A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ICTRP)
Öffentlicher Titel
Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor (ICTRP)
Untersuchte Krankheit(en)
Acute Intracranial Hemorrhage (ICTRP)
Untersuchte Intervention
Drug: andexanet alfa;Drug: Usual Care (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:
1. 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 EU General Data Protection Regulation (GDPR) and
national and local regulations.
2. Age = 18 years old 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 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 documented
anti fXa activity is > 100 ng/mL for direct fXa inhibitors (apixaban,
rivaroxaban or edoxaban) may be enrolled, irrespective of the time of the last
dose, and 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 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.
Exclusion Criteria
If a patient meets any of the following criteria, he or 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 and that are not expected to significantly affect
hematoma volume are allowed (e.g., Burr holes for intracranial pressure monitoring,
endoscopy, bronchoscopy, central lines.
2. 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
intubated/sedated for non-neurologic reasons within 2 hours prior to consent.
3. Purposefully left blank.
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.
7. Acute decompensated heart failure or cardiogenic shock at the time of randomization.
8. Severe sepsis or septic shock at the time of randomization.
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:
1. VKA (e.g., warfarin).
2. Dabigatran.
3. 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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Number of Participants Who Achieved Effective Hemostasis (ICTRP)
Percentage Change From Baseline to Nadir in Anti-FXa Activity (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Alexion Pharmaceuticals, Inc., clinicaltrials@alexion.com, 1-855-752-2356 (ICTRP)
Sekundäre IDs
2018-002620-17, 18-513 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT03661528 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar