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Trial of Andexanet in ICH Patients Receiving an Oral FXa Inhibitor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03661528
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : December 24, 2019
Population Health Research Institute
Information provided by (Responsible Party):
Portola Pharmaceuticals

Brief Summary:
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 or disease Intervention/treatment Phase
Acute Intracranial Hemorrhage Drug: andexanet alfa Phase 4

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 12 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 440 patients are planned to be enrolled in the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4 Randomized Clinical Trial of Andexanet Alfa [Andexanet Alfa for Injection] in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor
Actual Study Start Date : January 18, 2019
Estimated Primary Completion Date : March 1, 2023
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Intervention Details:
  • Drug: andexanet alfa
    Andexanet is a recombinant version of human FXa

Primary Outcome Measures :
  1. Proportion of patients with good or excellent hemostatic efficacy as rated by an independent adjudication committee [ Time Frame: 12 hours ]

Secondary Outcome Measures :
  1. Change from baseline in anti-fXa activity [ Time Frame: 1-3 hours ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  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.
  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.

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 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:

    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®).
  12. Past or planned use of andexanet.
  13. Treatment with an investigational drug < 30 days prior to consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03661528

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Contact: Study Clinical Trial Contact 650-246-7000

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Sponsors and Collaborators
Portola Pharmaceuticals
Population Health Research Institute

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Responsible Party: Portola Pharmaceuticals Identifier: NCT03661528    
Other Study ID Numbers: 18-513
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: December 24, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Portola Pharmaceuticals:
acute intracranial hemorrhage
Additional relevant MeSH terms:
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Intracranial Hemorrhages
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases