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

NCT04233073 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: ALXN2070-19-515
• Study Type: interventional
• Target: 10
• Locations: 6 countries
• Sites: 56

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.

Conditions

Surgery

Keywords

Urgent Surgery; Thrombosis; Anticoagulant; Surgery; Surgical; Abdominal; Thoracic; Orthopedic; Gynecological; Laparoscopic; Neurosurgery; Gastrointestinal

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (1)

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

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

Interventions

andexanet alfa DRUG

Andexanet is a recombinant version of human FXa

Also known as: Andexxa®, Ondexxya®

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (56)

Clinical Trial Site

Phoenix, Arizona, 85006, United States

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Tucson, Arizona, 85724, United States

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Long Beach, California, 90806, United States

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Moreno Valley, California, 92555, United States

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Washington D.C., District of Columbia, 20037, United States

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Sarasota, Florida, 34239, United States

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Tampa, Florida, 33606, United States

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Iowa City, Iowa, 52242, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02114, United States

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Camden, New Jersey, 08103, United States

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Staten Island, New York, 10305, United States

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Charlotte, North Carolina, 28203, United States

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Durham, North Carolina, 27710, United States

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Columbus, Ohio, 43210, United States

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Tulsa, Oklahoma, 74104, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Klagenfurt, 9020, Austria

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Vienna, 1090, Austria

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Clermont-Ferrand, 63003, France

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Dijon, 21070, France

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Lille, 59037, France

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Nantes, 44093, France

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Paris, 75012, France

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Paris, 75679, France

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Aachen, 52074, Germany

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Bonn, 53127, Germany

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Cologne, 51109, Germany

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Dortmund, 44137, Germany

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Freiburg im Breisgau, 79106, Germany

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Giessen, 35392, Germany

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Heidelberg, 69120, Germany

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Konstanz, 78464, Germany

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Mainz, 55131, Germany

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Murnau am Staffelsee, 82418, Germany

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Würzburg, 97080, Germany

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Ashkelon, 7830604, Israel

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Haifa, 3109601, Israel

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Jerusalem, 9103102, Israel

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Jerusalem, 92100, Israel

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Petah Tikva, 4941492, Israel

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Kamakura, 247-8533, Japan

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Kasuga, 816-0864, Japan

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Kawasaki, 216-8511, Japan

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Kumamoto, 860-0008, Japan

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Kumamoto, 861-8520, Japan

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Kurume, 830-8543, Japan

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Nagoya, 466-8650, Japan

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Sakai, 593-8304, Japan

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Sendai, 980-8574, Japan

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Tokyo, 113-8602, Japan

Location

Related Publications (1)

• 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.

  PMID: 37314165 DERIVED

MeSH Terms

Conditions

Thrombosis

Interventions

PRT064445

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

The study was terminated early due to the limited value as a single-arm study.

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

+1-855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 18, 2020
• Study Start: June 27, 2021
• Primary Completion: November 23, 2021
• Study Completion: January 25, 2022
• Last Updated: March 22, 2023
• Results First Posted: March 22, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

AU (4); DE (11); IL (5); US (20); JP (10); FR (6)