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SurgeryPhase 2Annexa-SNCT04233073

Trial of Andexanet in Patients Receiving an Oral FXa Inhibitor Who Require Urgent Surgery

A Phase 2 study testing andexanet alfa in people with Surgery, run by Alexion Pharmaceuticals, Inc. at 56 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 84 years
Conditions the study is for
Surgery
What is being tested?
andexanet alfa
How many people
10 participants
Where
56 sitesin 6 countries
Study dates
27 Jun 2021to 25 Jan 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 84 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • > 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).

Who cannot join

  • 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:
  • 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.
  • 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.
  • The patient has acute bleeding in a critical area or organ, such as pericardial, intracranial, or intraspinal.
Show all 28Show fewer
  • 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.

Trial locations and contacts

56 sites in 6 countries.

56 sites in 6 countries

United States20 sites

  • Clinical Trial Site

    Boston, Massachusetts, 02111

  • Clinical Trial Site

    Boston, Massachusetts, 02114

  • Clinical Trial Site

    Camden, New Jersey, 08103

  • Clinical Trial Site

    Charlotte, North Carolina, 28203

  • Clinical Trial Site

    Columbus, Ohio, 43210

  • Clinical Trial Site

    Durham, North Carolina, 27710

  • Clinical Trial Site

    Iowa City, Iowa, 52242

  • Clinical Trial Site

    Long Beach, California, 90806

  • Clinical Trial Site

    Moreno Valley, California, 92555

  • Clinical Trial Site

    Philadelphia, Pennsylvania, 19104

  • Clinical Trial Site

    Phoenix, Arizona, 85006

  • Clinical Trial Site

    Pittsburgh, Pennsylvania, 15212

  • Clinical Trial Site

    Pittsburgh, Pennsylvania, 15213

  • Clinical Trial Site

    Portland, Oregon, 97239

  • Clinical Trial Site

    Sarasota, Florida, 34239

  • Clinical Trial Site

    Staten Island, New York, 10305

  • Clinical Trial Site

    Tampa, Florida, 33606

  • Clinical Trial Site

    Tucson, Arizona, 85724

  • Clinical Trial Site

    Tulsa, Oklahoma, 74104

  • Clinical Trial Site

    Washington D.C., District of Columbia, 20037

Other trials in United States

Germany11 sites

  • Clinical Trial Site

    Aachen, 52074

  • Clinical Trial Site

    Bonn, 53127

  • Clinical Trial Site

    Cologne, 51109

  • Clinical Trial Site

    Dortmund, 44137

  • Clinical Trial Site

    Freiburg im Breisgau, 79106

  • Clinical Trial Site

    Giessen, 35392

  • Clinical Trial Site

    Heidelberg, 69120

  • Clinical Trial Site

    Konstanz, 78464

  • Clinical Trial Site

    Mainz, 55131

  • Clinical Trial Site

    Murnau am Staffelsee, 82418

  • Clinical Trial Site

    Würzburg, 97080

Other trials in Germany

Japan10 sites

  • Clinical Trial Site

    Kamakura, 247-8533

  • Clinical Trial Site

    Kasuga, 816-0864

  • Clinical Trial Site

    Kawasaki, 216-8511

  • Clinical Trial Site

    Kumamoto, 860-0008

  • Clinical Trial Site

    Kumamoto, 861-8520

  • Clinical Trial Site

    Kurume, 830-8543

  • Clinical Trial Site

    Nagoya, 466-8650

  • Clinical Trial Site

    Sakai, 593-8304

  • Clinical Trial Site

    Sendai, 980-8574

  • Clinical Trial Site

    Tokyo, 113-8602

Other trials in Japan

France6 sites

  • Clinical Trial Site

    Clermont-Ferrand, 63003

  • Clinical Trial Site

    Dijon, 21070

  • Clinical Trial Site

    Lille, 59037

  • Clinical Trial Site

    Nantes, 44093

  • Clinical Trial Site

    Paris, 75012

  • Clinical Trial Site

    Paris, 75679

Other trials in France

Israel5 sites

  • Clinical Trial Site

    Ashkelon, 7830604

  • Clinical Trial Site

    Haifa, 3109601

  • Clinical Trial Site

    Jerusalem, 9103102

  • Clinical Trial Site

    Jerusalem, 92100

  • Clinical Trial Site

    Petah Tikva, 4941492

Other trials in Israel

Austria4 sites

  • Clinical Trial Site

    Graz, 8036

  • Clinical Trial Site

    Innsbruck, 6020

  • Clinical Trial Site

    Klagenfurt, 9020

  • Clinical Trial Site

    Vienna, 1090

Other trials in Austria

About this study

Official title: 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.

Read the 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.

Conditions
Surgery
Being tested
andexanet alfa
Keywords
Urgent Surgery, Thrombosis, Anticoagulant, Surgery, Surgical, Abdominal, Thoracic, Orthopedic, Gynecological, Laparoscopic, Neurosurgery, Gastrointestinal
Medical subject headings
Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • andexanet alfaDrug

    Also called Andexxa®, Ondexxya®

    Andexanet is a recombinant version of human FXa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Achieving Effective Hemostasis

    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.

    Measured: Hemostasis will be assessed from the start of surgery to the end of the procedure

Secondary outcomes (1)

  1. Percent Change From Baseline In Anti-fXa Activity To Treatment Nadir

    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.

    Measured: Baseline, Treatment nadir (not to exceed a total of 6.5 hours of andexanet dosing)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start27 Jun 2021
  3. Primary completion23 Nov 2021
  4. Study completion25 Jan 2022

Why it stopped: Limited value as a single-arm study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04233073
Sponsor's protocol ID
ALXN2070-19-515
Acronym
Annexa-S
Status last verified
Feb 2023
First submitted
14 Jan 2020
Last updated
22 Mar 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

Publications

  • Schulman S, Bhagirath V, Chan N, Germini F, Ikesaka R, Iorio A, Mithoowani S, Weitz JI, Gross PL. Prothrombin complex concentrate for emergency surgery in patients on oral Xa-inhibitors. J Thromb Haemost. 2024 Oct;22(10):2761-2766. doi: 10.1016/j.jtha.2024.07.002. Epub 2024 Jul 11.

    PubMed 39002730

  • Levy JH, Mamoun N. Direct oral anticoagulants and their antagonists in perioperative practice. Curr Opin Anaesthesiol. 2023 Aug 1;36(4):394-398. doi: 10.1097/ACO.0000000000001275. Epub 2023 Jun 6.

    PubMed 37314165

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing andexanet alfa in people with Surgery, run by Alexion Pharmaceuticals, Inc. at 56 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States, Germany, Japan, France, Israel and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Achieving Effective Hemostasis (time frame: Hemostasis will be assessed from the start of surgery to the end of the procedure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04233073, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2023.

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