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

February 24, 2023 updated by: Alexion

Prospective, Open-Label Clinical Study of Andexanet Alfa in Patients Receiving FXa (Activated Factor X) Inhibitor Who Require Urgent Surgery

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Clinical Trial Site
      • Innsbruck, Austria, 6020
        • Clinical Trial Site
      • Klagenfurt am Wörthersee, Austria, 9020
        • Clinical Trial Site
      • Wien, Austria, 1090
        • Clinical Trial Site
  • France
      • Clermont-Ferrand, France, 63003
        • Clinical Trial Site
      • Dijon, France, 21070
        • Clinical Trial Site
      • Lille, France, 59037
        • Clinical Trial Site
      • Nantes, France, 44093
        • Clinical Trial Site
      • Paris, France, 75012
        • Clinical Trial Site
      • Paris, France, 75679
        • Clinical Trial Site
  • Germany
      • Aachen, Germany, 52074
        • Clinical Trial Site
      • Bonn, Germany, 53127
        • Clinical Trial Site
      • Dortmund, Germany, 44137
        • Clinical Trial Site
      • Freiburg, Germany, 79106
        • Clinical Trial Site
      • Gießen, Germany, 35392
        • Clinical Trial Site
      • Heidelberg, Germany, 69120
        • Clinical Trial Site
      • Konstanz, Germany, 78464
        • Clinical Trial Site
      • Köln, Germany, 51109
        • Clinical Trial Site
      • Mainz, Germany, 55131
        • Clinical Trial Site
      • Murnau Am Staffelsee, Germany, 82418
        • Clinical Trial Site
      • Würzburg, Germany, 97080
        • Clinical Trial Site
  • Israel
      • Ashkelon, Israel, 7830604
        • Clinical Trial Site
      • Haifa, Israel, 3109601
        • Clinical Trial Site
      • Jerusalem, Israel, 9103102
        • Clinical Trial Site
      • Jerusalem, Israel, 92100
        • Clinical Trial Site
      • Petah Tikva, Israel, 4941492
        • Clinical Trial Site
  • Japan
      • Kamakura, Japan, 247-8533
        • Clinical Trial Site
      • Kasuga, Japan, 816-0864
        • Clinical Trial Site
      • Kawasaki, Japan, 216-8511
        • Clinical Trial Site
      • Kumamoto, Japan, 860-0008
        • Clinical Trial Site
      • Kumamoto, Japan, 861-8520
        • Clinical Trial Site
      • Kurume, Japan, 830-8543
        • Clinical Trial Site
      • Nagoya, Japan, 466-8650
        • Clinical Trial Site
      • Sakai, Japan, 593-8304
        • Clinical Trial Site
      • Sendai, Japan, 980-8574
        • Clinical Trial Site
      • Tokyo, Japan, 113-8602
        • Clinical Trial Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Clinical Trial Site
      • Tucson, Arizona, United States, 85724
        • Clinical Trial Site
    • California
      • Long Beach, California, United States, 90806
        • Clinical Trial Site
      • Moreno Valley, California, United States, 92555
        • Clinical Trial Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • Clinical Trial Site
    • Florida
      • Sarasota, Florida, United States, 34239
        • Clinical Trial Site
      • Tampa, Florida, United States, 33606
        • Clinical Trial Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Clinical Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Clinical Trial Site
      • Boston, Massachusetts, United States, 02111
        • Clinical Trial Site
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Clinical Trial Site
    • New York
      • Staten Island, New York, United States, 10305
        • Clinical Trial Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Clinical Trial Site
      • Durham, North Carolina, United States, 27710
        • Clinical Trial Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Clinical Trial Site
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
        • Clinical Trial Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Clinical Trial Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Clinical Trial Site
      • Pittsburgh, Pennsylvania, United States, 15212
        • Clinical Trial Site
      • Pittsburgh, Pennsylvania, United States, 15213
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 84 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Achieving Effective Hemostasis
Time Frame: Hemostasis will be assessed from the start of surgery to the end of the procedure
Effective hemostasis is defined as excellent or good as assessed by the Investigator; Ineffective hemostasis is defined as moderate or poor as assessed by the Investigator. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Hemostasis will be assessed from the start of surgery to the end of the procedure

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline In Anti-fXa Activity To Treatment Nadir
Time Frame: Baseline, Treatment nadir (not to exceed a total of 6.5 hours of andexanet dosing)
Baseline is defined as the last non-missing value on or before first study drug administration. On treatment nadir is the minimum value of anti-fXa activity during the period of time from the end of the andexanet bolus to the end of the andexanet infusion. All data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
Baseline, Treatment nadir (not to exceed a total of 6.5 hours of andexanet dosing)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alexion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 27, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 23, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 25, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 14, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 18, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 22, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 24, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALXN2070-19-515

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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