Apixaban for Secondary Prevention of Thromboembolism Among Patients With AntiphosPholipid Syndrome

NCT02295475 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: CV185-3571040354
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

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".

Conditions

Antiphospholipid Syndrome; Thrombosis

Keywords

Apixaban; Eliquis

Outcome Measures

Primary Outcomes (2)

• Rate (number divided by duration) of clinically overt thromboses (arterial and/or venous) or vascular death

  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

  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 Outcomes (1)

• Net clinical benefit (combination of occurrence of thrombosis and bleeding rates)

  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

Study Arms (2)

Apixaban

EXPERIMENTAL

Subjects will receive apixaban 5 mg tablets taken twice daily for the duration of the study.

Drug: Apixaban

Warfarin

ACTIVE COMPARATOR

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

Interventions

Apixaban DRUG

Also known as: Eliquis

Apixaban

Warfarin DRUG

Also known as: Coumadin

Warfarin

Eligibility Criteria

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

You may qualify if:

• Be ≥ 18 years of age
• 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;
• 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).
• Able to undergo magnetic resonance imaging (MRI) of the brain;
• 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;
• Be willing to provide informed consent to contact the subjects anticoagulation provider for INRs and dosing as well as details regarding any adverse events;
• 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;
• Women must not be breastfeeding;
• 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;
• 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;
• 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;
• 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.

You may not qualify if:

• A history of arterial thromboembolism (e.g., stroke, myocardial infarction, or other arterial thrombosis);
• Another indication for long-term anticoagulation for which no FDA (Food \& Drug Administration) approval of apixaban exists (e.g., mechanical heart valve);
• A life expectancy of less than 1 year;
• Is unable to attend follow-up appointments;
• Is participating in a clinical trial or has participated in a trial within the last 30 days;
• Is receiving concomitant dual antiplatelet therapy;
• Requires aspirin dose of greater than 165 mg daily;
• Requires clopidogrel, ticagrelor, prasugrel, or another P2Y12 inhibitor;
• A hemoglobin level of less than 8 mg per deciliter;
• A platelet count of less than 50,000 per cubic millimeter;
• Serum creatinine level of more than 2.5 mg per deciliter or a calculated creatinine clearance of less than 25 ml per minute;
• Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range;
• A total bilirubin more than 1.5 times the upper limit of the normal range;
• Have active cancer for which treatment (chemotherapy/radiation therapy) is being delivered or has been delivered within the last 3 months;
• Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as:

Sponsors & Collaborators

• Scott C. Woller, MD: lead
• Bristol-Myers Squibb: collaborator
• University of Utah: collaborator

Study Sites (2)

The James Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

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MeSH Terms

Conditions

Antiphospholipid Syndrome; Thrombosis

Interventions

apixaban; Warfarin

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Scott C Woller, MD

  Intermountain Health Care, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-Director Thrombosis Program

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 20, 2014
• Study Start: December 10, 2014
• Primary Completion: April 1, 2020
• Study Completion: March 1, 2022
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)