Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome

This pilot study has two primary aims. The first is to identify patients with a clinical
diagnosis of APS and then describe their recruitment, enrollment, screening failure rate,
adherence to therapy, clinical characteristics, and APS diagnostic criteria in terms of
broadly accepted published standards. Essential in this aim is capture of ability to
identify, recruit, randomize, and retain patients with APS receiving a direct oral
anticoagulant. We will also report compliance and patient satisfaction; central to durable
anticoagulation management.

The second aim is to report rates of thrombosis (arterial or venous) and death caused by
thrombosis, as well as major bleeding plus clinically relevant non-major bleeding over one
year among APS patients randomized to either warfarin or apixaban. As such, we will report
the rate of Thrombosis (arterial and/or venous) [ Time Frame: Up to 13 months after
enrollment ] [ Designated as safety issue: No ] and Major and non-major bleeding [ Time
Frame: Up to 13 months after enrollment ] [ Designated as safety issue: Yes ]

Inclusion Criteria:

1. Be ≥ 18 years of age

2. Have a clinical diagnosis of the APS for which the patient is receiving
anticoagulation therapy for the secondary prevention of thrombosis

2.a. Anticoagulation is defined as warfarin sodium titrated at the discretion of the
clinician to a target INR 2.5 (range 2-3), 3.0 (range 2.5-3.5), or 3.5 (range 3-4).

2. b. Should the patient be receiving some other form of anticoagulation (apixaban,
rivaroxaban, edoxaban, dabigatran etexilate, low-molecular weight heparin) and are willing
to be randomized to warfarin with a target INR 2.5 or apixaban 5 mg PO BID and they meet
all other inclusion criteria

3. Have completed at least 6months of anticoagulation for the indication of thrombosis and
are without acute neurologic symptoms consistent with thrombosis, CVA, or TIA for a minimum
of six months.

4. Be willing to provide informed consent to contact the subjects anticoagulation provider
for INRs and dosing as well as details regarding any adverse events

5. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the
start of study drug.

6. Women must not be breastfeeding

7. Women of childbearing potential 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.

8. Males who are sexually active with women of childbearing potential 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.

9. Azoospermic males and women of childbearing potential who are continuously not
heterosexually active are exempt from contraceptive requirements. However they must still
undergo pregnancy testing.

10. Be willing to undergo magnetic resonance imaging (MRI) of the brain

Exclusion Criteria:

1. Another indication for long-term anticoagulation for which no FDA approval of apixaban
exists (e.g. mechanical heart valve)

2. A life expectancy of less than 1 year

3. Is unable to attend follow-up appointments

4. Is participating in a conflicting clinical trial or has participated in a trial within
the last 30 days

5. Is receiving concomitant dual antiplatelet therapy

6. Requires aspirin dose of greater than 165mg daily

7. A hemoglobin level of less than 8 mg per deciliter

8. A platelet count of less than 50,000 per cubic millimeter

9. Serum creatinine level of more than 2.5 mg per deciliter (221 μmol per liter) or a
calculated creatinine clearance of less than 25 ml per minute

10. Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the
upper limit of the normal range

11. A total bilirubin more than 1.5 times the upper limit of the normal range.

12. Have active cancer for which treatment (chemotherapy/radiation therapy) is being
delivered or has been delivered within the last 3 months

13. Are actively receiving a strong dual inhibitor of CYP3A4 and P-gp, such as:

13.a Ketoconazole 13.b Itraconazole 13.c Ritonavir 13.d clarithromycin

14. Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as: 14.a rifampin
14.b carbamazepine 14.c phenytoin 14.d St. John's wort

15. Intend pregnancy or breastfeeding within the next year

16. Have a known allergy to apixaban, rivaroxaban, or edoxaban

17. Have experienced thrombosis while receiving warfarin at a target INR of 2-3 and have
been assigned a higher target INR at the discretion of their clinician.

18. Patients with active pathological bleeding.

19. A history of arterial thromboembolism (e.g., stroke, myocardial infarction or other
arterial thrombosis)

20. Requires clopidogrel, tigacrolor, prasugrel, or another P2Y12 inhibitor

21. Have a history of catastrophic APS (CAPS) as defined by clinical routine

22. Have radiographic evidence of prior arterial thrombosis on MRI as defined per clinical
routine upon screening MRI

23. At the discretion of the investigator are considered to not be candidates secondary to
s a safety concern.