Apixaban for Secondary Prevention of Thromboembolism Among Patients With AntiphosPholipid Syndrome (ASTRO-APS)

September 26, 2023 updated by: Scott C. Woller, MD

Apixaban for the Secondary Prevention of Thromboembolism: a Prospective Randomized Outcome Pilot Study Among Patients With the AntiphosPholipid Syndrome

This study is designed to compare the safety and effectiveness of two blood thinners, apixaban and warfarin, for the prevention of blood clots in patients who have a higher risk of blood clots than the general population, a condition called "antiphospholipid syndrome".

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a prospective, open-label, blinded event, pilot study that will randomize patients with a history of venous thrombosis and antiphospholipid syndrome (APS) already receiving anticoagulation to either warfarin or apixaban. The study will assess the safety and efficacy of apixaban compared with adjusted dose warfarin for the prevention of recurrent thrombosis (defined as the aggregate of arterial or venous thrombosis) and vascular death. The primary efficacy outcome will be confirmed upon adjudication by a panel blinded to the treatment arm. The primary safety outcome will be major bleeding and clinically relevant non-major bleeding events. Patients who consent to study participation will be randomized to anticoagulation with adjusted dose warfarin sodium or apixaban 5 mg by mouth twice daily. This pilot study will also provide information and experience identifying, recruiting, enrolling and randomizing patients with APS and a history of venous thrombosis to anticoagulation with apixaban or warfarin for the prevention of recurrent thrombosis.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 4

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

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The James Comprehensive Cancer Center
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center

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

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Be ≥ 18 years of age

  2. Have a clinical diagnosis of the antiphospholipid syndrome (APS) and a history of venous thrombosis only (excluding arterial thrombosis as recommended by the Data Safety Monitoring Board (DSMB)) for which the patient is receiving anticoagulation therapy for the prevention of recurrent thrombosis;

    1. Anticoagulation is defined as warfarin sodium titrated at the discretion of the clinician to a target INR (International Normalized Ratio) 2.5 (range 2-3), 3.0 (range 2.5-3.5), or 3.5 (range 3-4).
    2. Should the patient be receiving some other form of anticoagulation (apixaban, rivaroxaban, edoxaban, dabigatran etexilate, low-molecular weight heparin) and is willing to be randomized to warfarin with a target INR 2.5 or apixaban 5 mg by mouth twice daily and meets all other inclusion criteria.
  3. Able to undergo magnetic resonance imaging (MRI) of the brain;
  4. Have completed at least 6 months of anticoagulation for the indication of venous thrombosis and be without symptoms or signs consistent with acute thrombosis for a minimum of 6 months;
  5. Be willing to provide informed consent to contact the subjects anticoagulation provider for INRs and dosing as well as details regarding any adverse events;
  6. A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG (Human Chorionic Gonadotropin) within 24 hours prior to the start of study drug;
  7. Women must not be breastfeeding;
  8. A WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of study drug apixaban (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion;
  9. Males who are sexually active with any WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of the study drug apixaban (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days post-treatment completion;
  10. Azoospermic males and women who are continuously not heterosexually active are exempt from contraceptive requirements. However, a WOCBP must still undergo pregnancy testing as described above;
  11. If they are actively receiving a strong dual inhibitor of cytochrome P450 3A4 (CYP3A4) and P-gp, such as ketoconazole, itraconazole, ritonavir, and are agreeable to taking apixaban 2.5 mg twice daily.

Exclusion Criteria:

  1. A history of arterial thromboembolism (e.g., stroke, myocardial infarction, or other arterial thrombosis);
  2. Another indication for long-term anticoagulation for which no FDA (Food & Drug Administration) approval of apixaban exists (e.g., mechanical heart valve);
  3. A life expectancy of less than 1 year;
  4. Is unable to attend follow-up appointments;
  5. Is participating in a clinical trial or has participated in a trial within the last 30 days;
  6. Is receiving concomitant dual antiplatelet therapy;
  7. Requires aspirin dose of greater than 165 mg daily;
  8. Requires clopidogrel, ticagrelor, prasugrel, or another P2Y12 inhibitor;
  9. A hemoglobin level of less than 8 mg per deciliter;
  10. A platelet count of less than 50,000 per cubic millimeter;
  11. Serum creatinine level of more than 2.5 mg per deciliter or a calculated creatinine clearance of less than 25 ml per minute;
  12. Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range;
  13. A total bilirubin more than 1.5 times the upper limit of the normal range;
  14. Have active cancer for which treatment (chemotherapy/radiation therapy) is being delivered or has been delivered within the last 3 months;

  15. Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as:

    • rifampin
    • carbamazepine
    • phenytoin
    • St.John's wort
  16. Intend pregnancy or breastfeeding within the next year;
  17. Have a known allergy to apixaban, rivaroxaban, or edoxaban;
  18. Have experienced thrombosis while receiving warfarin at a target INR of 2 to 3 and have been assigned a higher target INR at the discretion of the treating clinician;
  19. Have active pathological bleeding;
  20. Have a history of catastrophic APS (CAPS) as defined by clinical routine;
  21. At the discretion of the investigator, are not considered to be good candidates secondary to a safety concern.

Patients who meet the above inclusion & exclusion criteria will be offered participation in the study. After informed consent is obtained, the patient will be consented for Magnetic Resonance Imaging (MRI). A brain MRI without contrast including weighted imaging and fluid-attenuated inversion recovery (FLAIR) will be performed as a study procedure to rule out prior stroke. If the patient has radiographic evidence of prior stroke on this MRI, then the patient will not be randomized, and will not be included in future study procedures or study analyses.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Apixaban
Subjects will receive apixaban 5 mg tablets taken twice daily for the duration of the study.
Drug: Apixaban
Other Names:
  • Eliquis
Active Comparator: Warfarin
Subjects will receive warfarin for the duration of the study, with the dose and frequency adjusted per clinician discretion to achieve an INR (International Normalized Ratio) between 2 and 4.
Drug: Warfarin
Other Names:
  • Coumadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate (number divided by duration) of clinically overt thromboses (arterial and/or venous) or vascular death
Time Frame: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment
From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment
Rate (number divided by duration) of occurrence of major (including fatal) and clinically relevant non-major bleeding
Time Frame: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment
Major bleeding is clinically overt bleeding accompanied by one or more of the following: a decrease in the hemoglobin level of 2 g per deciliter or more, transfusion of 2 or more units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding. Clinically relevant non-major bleeding is defined as clinically overt bleeding that does not satisfy the criteria for major bleeding and that led to hospital admission, physician-guided medical or surgical treatment, or a change in antithrombotic therapy.
From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Net clinical benefit (combination of occurrence of thrombosis and bleeding rates)
Time Frame: From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment
Sum of number of thrombosis and bleeding events divided by duration
From time of first dose of study drug through 2 days after receiving the last dose of study drug at the end of 12 months of treatment

Collaborators and Investigators

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

Sponsor

Scott C. Woller, MD

Collaborators

Bristol-Myers Squibb
University of Utah

Investigators

  • Principal Investigator: Scott C Woller, MD, Intermountain Health Care, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

December 10, 2014

Primary Completion (Actual)

April 1, 2020

Study Completion (Actual)

March 1, 2022

Study Registration Dates

First Submitted

November 18, 2014

First Submitted That Met QC Criteria

November 19, 2014

First Posted (Estimated)

November 20, 2014

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 26, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CV185-357
  • 1040354 (Other Identifier: Intermountain Healthcare IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Clinical Trials on Thrombosis

Clinical Trials on Warfarin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Serbia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe