Purpose

Randomized, controlled clinical trial evaluating the efficacy and safety of andexanet versus usual standard of care in patients with intracranial hemorrhage anticoagulated with a direct oral anticoagulant

Condition

Eligibility

Eligible Ages
Between 18 Years and 89 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.
  2. 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.
  3. 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 GCP, the Data Protection Directive (Directive 95/46/EC) and national and local regulations.
  4. Age 18 to <90 years old at the time of consent.
  5. An acute intracerebral bleeding episode, defined as an estimated blood volume > 0 to ≤ 60 mL acutely observed radiographically within the cerebrum. Patients may have extracerebral (e.g., subdural, subarachnoid) 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.
  6. Performance of a head CT or MRI scan demonstrating the intracerebral bleeding within 2 hours prior to randomization (the baseline scan may be repeated to meet this criterion).
  7. 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]):
  8. ≤ 15 hours prior to randomization.
  9. > 15 hours prior to randomization or unknown time of last dose, if documented anti fXa activity is > 100 ng/mL (or over the equivalent IU/mL threshold on a LMWH assay; see Laboratory Manual) within 2 hours prior to consent. Note: Patients enrolled in this manner should receive a high andexanet dosing regimen.
  10. 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 second baseline imaging scan.)
  11. Willingness to use medically acceptable methods of contraception through 30 days following study drug dose (for female and male subjects who are fertile).
  12. Have a negative pregnancy test documented prior to enrollment (for women of childbearing potential).

Exclusion Criteria

  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— Section 7.3 and Appendix F).
  2. Glasgow Coma Scale (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. Any bleeding into the epidural space.
  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:

o 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 (see Appendix G for DIC scoring algorithm).

7. Acute decompensated heart failure or cardiogenic shock at the time of randomization (see Appendix H for cardiogenic shock definition).

8. Severe sepsis or septic shock at the time of randomization (see Appendix H 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:

1. Vitamin K Antagonist (VKA) (e.g., warfarin).

2. Dabigatran.

3. Prothrombin Complex Concentrate products (PCC, e.g., KCentra®) or recombinant factor VIIa (rfVIIa) (e.g., NovoSeven®), or anti-inhibitor coagulant complex (e.g., FEIBA®).

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.

15. National Institutes of Health Stroke Scale (NIHSS) score >35 at the time of consent.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
Portola Pharmaceuticals

Study Contact

Study Clinical Trial Contact
650-246-7000
ClinicalTrials@portola.com

Detailed Description

This is a randomized, multicenter clinical trial designed to determine the efficacy and safety of andexanet compared to usual care in patients presenting with acute intracranial hemorrhage within 6 hours of symptom onset and within 15 hours of taking an oral factor Xa inhibitor. The study will use a prospective, randomized, open label (PROBE) design. The primary efficacy outcome will be adjudicated by a blinded Endpoint Adjudication Committee. To support the adjudication of hemostatic efficacy, a blinded Imaging Core Laboratory will review all available scans. Approximately 900 patients are planned to be enrolled in the study.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.