Andexanet Alfa for the treatment of brain hemorrhages in patients taking anticoagulant medications.

Austria, Belgium, Canada, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States (ICTRP)

ID di studio ICTRP
NCT03661528 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
non disponibile

Titolo accademico
A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ICTRP)

Titolo pubblico
Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor (ICTRP)

Malattie studiate
Acute Intracranial Hemorrhage (ICTRP)

Intervento studiato
Drug: andexanet alfa;Drug: Usual Care (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor). (ICTRP)

Criteri di inclusione/esclusione
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)

non disponibile

Endpoint primari e secondari
Number of Participants Who Achieved Effective Hemostasis (ICTRP)

Percentage Change From Baseline to Nadir in Anti-FXa Activity (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Alexion Pharmaceuticals, Inc., clinicaltrials@alexion.com, 1-855-752-2356 (ICTRP)

ID secondari
2018-002620-17, 18-513 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT03661528 (ICTRP)