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19-515 ANNEXA-S


Title PROSPECTIVE, OPEN-LABEL STUDY OF ANDEXANET ALFA IN PATIENTS RECEIVING A FACTOR XA INHIBITOR WHO REQUIRE URGENT SURGERY (ANNEXA-S)
Therapeutic Area Trauma
Principal Investigator Nikolay Bugaev, MD
Min Age 18 Years
Max Age 85 Years
Gender Any
Contact Nikolay Bugaev
617-636-4488
nbugaev@tuftsmedicalcenter.org
More Information https://clinicaltrials.gov/ct2/show/NCT04233073

Overview

In patients requiring urgent surgery who are being treated with a direct or indirect Factor Xa (FXa) inhibitor, the objectives of this study are as follows:
Primary Objective:
• To evaluate hemostatic efficacy following andexanet alfa (andexanet) treatment.

Secondary Efficacy Objective:
• To evaluate the effect of andexanet on anti-fXa activity.

Exploratory Efficacy Objectives:
• To evaluate the effect of andexanet on thrombin generation (TG).
• To evaluate the use of red blood cell (RBC) transfusions.
• To evaluate the use of non-RBC, non-platelet blood products and hemostatic agents.
• To evaluate the transfusion-corrected change in hemoglobin from baseline to the nadir.
• To evaluate the time from obtaining informed consent (study consent) to the start of surgery.
• To evaluate observed intraoperative blood loss and the difference between predicted versus observed blood loss.
• To evaluate the length of index hospitalization, intensive care unit (ICU) stay, time in a post-anesthesia care unit (PACU), time in the operating room (OR), and length of surgery.
• To evaluate the occurrence of re-hospitalization.
• To evaluate the occurrence of post-surgical major bleeding.
• To evaluate the occurrence of re-operations for bleeding.
• To evaluate the effect of andexanet on tissue factor pathway inhibitor (TFPI) activity.
• In patients receiving enoxaparin, to evaluate the effect of andexanet on anti-IIa activity.

Safety Objective:
• To evaluate the overall safety of andexanet.

Study Details

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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

Study Requirements

The following screening procedures will be done to help the study doctor determine if you qualify for this study:

 

  • Informed Consent
  • Demographics (age, race, ethnicity, gender)
  • Medical History
  • Physical examination
  • Review medications you have taken (including details about the last time you took a Factor Xa inhibitor blood thinner drug and which one was taken)
  • Vital signs (for example, checking your blood pressure and pulse) and weight
  • Blood samples collected for laboratory testing. If you are female, some of your blood may be used for a pregnancy test.

Physical Examination

A focused physical examination will be performed on all subjects at various time points before and after the surgical procedure.  The examination will include, at a minimum, any part relevant to your surgery and an assessment of the surgical incision site.

 

On-Study Procedures:

 

The following study related procedures will be done during your surgery and while you are receiving the study drug:

 

  • Vital signs (for example, checking your blood pressure and pulse)
  • Physical examination
  • Blood samples collected for laboratory testing
  • Receive intravenous andexanet
  • Assessment of andexanet’s effects by the study doctor and study staff
  • Record adverse events, medications you have taken, and study assessments

 

BLOOD COLLECTIONs

Blood samples will be taken from a vein about 27 times during the study. Approximately 238.5 milliliters of blood (about 16 tablespoons) will be taken over the total time you are in the study (about 30-37 days). Each blood sample will be taken from either a small hollow tube already placed in your vein (IV) or some may require a new needle stick.

 

Follow-up Visits:

 

The following study related procedures will be done during follow-up visits:

 

  • Physical examination
  • Blood samples collected for laboratory testing
  • Record adverse events, medication administered, and study assessments

 

Your participation in this study will last about 30-37 days. You will stay in the hospital for as long as your study doctors think you need to and this is not affected by whether you join the study. However, whether or not you are still in the hospital, you will have follow-up visits for the study in about 2, 3, and 30 days after you are enrolled. If you have been discharged from the hospital, you must return to the hospital to undergo the remainder of these follow-up study visits.  You may also have unscheduled visits if the study doctor thinks they are necessary