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Trial of Andexanet in Patients Receiving an Oral FXa Inhibitor Who Require Urgent Surgery (Annexa-S)

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ClinicalTrials.gov Identifier: NCT04233073
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : October 7, 2021
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
Prospective, open-label clinical trial to evaluate the efficacy and safety of andexanet alfa patients who require urgent surgery that have been anticoagulated with the FXa (activated factor X) inhibitors.

Condition or disease Intervention/treatment Phase
Surgery Drug: andexanet alfa Phase 2

Detailed Description:
This is a multicenter, prospective, open-label study to determine the efficacy and safety of andexanet in patients who require urgent surgery who have received 1 of the following FXa inhibitors: apixaban, rivaroxaban, edoxaban, or enoxaparin. The start of surgery must be within 15 hours following the last dose of FXa inhibitor. The primary efficacy outcome will be adjudicated by an independent Endpoint Adjudication Committee.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective, Open-Label Clinical Study of Andexanet Alfa in Patients Receiving FXa (Activated Factor X) Inhibitor Who Require Urgent Surgery
Actual Study Start Date : May 11, 2021
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : October 31, 2022

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: andexanet alfa
    Andexanet is a recombinant version of human FXa
    Other Names:
    • Andexxa®
    • Ondexxya®


Primary Outcome Measures :
  1. Proportion of patients with good or excellent intraoperative hemostatic efficacy as determined by the surgeon's assessment and confirmed by an independent adjudication committee [ Time Frame: At the end of surgery, not to exceed a total of 6.5 hours of andexanet dosing ]

Secondary Outcome Measures :
  1. Percent change from baseline in anti-fXa activity [ Time Frame: At the end of surgery, not to exceed a total of 6.5 hours of andexanet dosing ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All of the following criteria must be met for the patient to be eligible:

  • Either the patient or their medical proxy (or legal designee) has given written informed consent.
  • Age ≥ 18 and < 85 years old.
  • Requires urgent surgical intervention that must occur within 12 hours of consent, for which reversal of anti-fXa activity is judged necessary.
  • Treatment with an oral FXa inhibitor (apixaban [last dose 2.5 mg or greater], rivaroxaban [last dose 10 mg or greater], edoxaban [last dose 30 mg or greater] or enoxaparin [≥ 1 mg/kg/d]):
  • ≤ 15 hours prior to start of surgery.
  • > 15 hours prior to start of surgery or unknown time from the last dose, if documented anti fXa activity is > 100 ng/mL (> 0.5 IU/mL for enoxaparin, or over the equivalent IU/mL threshold on a low molecular weight heparin assay; see Laboratory Manual) within 2 hours prior to consent. Note: Patients enrolled in this manner should receive a high-andexanet dosing regimen.
  • Have a negative pregnancy test documented prior to enrollment (for women of childbearing potential).
  • Willingness to use highly effective methods of contraception through 30 days following study drug dose (for female and male patients who are fertile).

Exclusion Criteria:

If a patient meets any of the following criteria, he or she is not eligible:

  • Surgery for which the risk of clinically meaningful uncontrolled or unmanageable bleeding is low.
  • Acute life-threatening bleeding (ISTH criteria) at the time of Screening:

    1. The patient has acute-overt bleeding that is potentially life-threatening, e.g., with signs or symptoms of hemodynamic compromise, such as severe hypotension, poor skin perfusion, mental confusion, low urine output that cannot be otherwise explained.
    2. The patient has overt bleeding associated with a fall in hemoglobin level by ≥2g/dL, OR, a hemoglobin ≤8 g/dL if no baseline hemoglobin is available.
    3. The patient has acute bleeding in a critical area or organ, such as pericardial, intracranial, or intraspinal.
  • Any surgical procedure that involves the intraoperative use of systemic, intravascular, unfractionated heparin.
  • Primary procedure for efficacy assessment is a non-surgical interventional procedure (e.g, lumbar puncture, skin biopsy, cardiac catheterization, endoscopic retrograde cholangio-pancreatography).
  • Expected survival of < 1 month due to comorbidity.
  • Known "Do Not Resuscitate" order or similar advanced directive.
  • The patient has a recent history (within 30 days prior to screening) of a diagnosed TE as follows: venous thromboembolism (including deep vein thrombosis, pulmonary embolism, intracardiac thrombus), myocardial infarction (including asymptomatic troponin elevations), disseminated intravascular coagulation, acute traumatic coagulopathy, cerebrovascular accident, transient ischemic attack, unstable angina pectoris hospitalization, or severe peripheral vascular disease.
  • Acute decompensated heart failure or cardiogenic shock at the time of screening.
  • The patient has sepsis or septic or severe hemorrhagic shock at the time of Screening.
  • The patient has heparin-induced thrombocytopenia (with or without thrombosis).
  • Inherited coagulopathy (e.g., anti-phospholipid antibody syndrome, protein C/S deficiency, Factor V Leiden) at time of Screening.
  • Platelet count < 80,000/µL at the time of Screening.
  • Last dose of apixaban < 2.5 mg, rivaroxaban < 10 mg, edoxaban < 30 mg, or enoxaparin 40 mg.
  • The patient is pregnant or a lactating female.
  • The patient has received any of the following drugs or blood products within 7 days of enrollment:

    • Vitamin K antagonists (e.g., warfarin).
    • Dabigatran.
    • Prothrombin complex concentrate products (e.g., Kcentra®) or recombinant factor VIIa (e.g., NovoSeven®).
    • Whole blood, plasma fractions. Note: Administration of tranexamic acid, platelets or packed red blood cells is not an exclusion criterion.
  • The patient was treated with an investigational drug < 30 days prior to Screening.
  • Prior treatment with andexanet.
  • Known hypersensitivity to any component of andexanet.
  • Known allergic reaction to hamster proteins.
  • Known or suspected (i.e., presumed positive) COVID-19-related illness at the time of Screening.

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 ClinicalTrials.gov identifier (NCT number): NCT04233073


Contacts
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Contact: Study Trial Contact 855-752-2356 clinicaltrials@alexion.com

Locations
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Sponsors and Collaborators
Alexion Pharmaceuticals
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04233073    
Other Study ID Numbers: ALXN2070-19-515
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: October 7, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: After study complete results will be provided or 30 days after approval
Access Criteria: Per Alexion Policy, see Alexionclinicaltrials.com

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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 Alexion Pharmaceuticals:
Urgent Surgery
Thrombosis
Anticoagulant
Surgery
Surgical
Abdominal
Thoracic
Orthopedic
Gynecological
Laparoscopic
Neurosurgery
Gastrointestinal