RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome

Inclusion Criteria

1. Patients must be confirmed as having persistent antiphospholipid antibodies (aPL), defined as: positivity of one or more aPL, i.e. lupus anticoagulant, IgG and/or IgM anticardiolipin and/or anti beta 2 glycoprotein I antibodies at >40 GPL or MPL units or > the 99th centile of normal, on two or more occasions, at least 12 weeks apart. See Appendix 3 and Exclusion criteria for more information.

2. One or more of: a) Ischaemic stroke; b) transient ischaemic attack (TIA) with evidence of either acute or chronic ischaemic injury on brain magnetic resonance imaging (MRI) (including diffusion-weighted magnetic resonance imaging (DWI) lesion(s), previous cortical or subcortical infarction(s), or white matter hyperintensities) and diagnosed by a clinician with expertise in stroke; c) brain infarcts (territorial or subcortical) or white matter hyperintensities (WMH) of presumed vascular origin on brain MRI, with or without cognitive impairment; and an expert clinical opinion that anticoagulation is a reasonable treatment option (with the aim of preventing ischaemic brain injury).

3. Patients must weigh ≥ 50kg and ≤ 135kg.

4. Women must be on adequate contraception, barrier or hormonal, unless postmenopausal or sterilised.

Exclusion Criteria

1. Patients who are triple positive for antiphospholipid antibodies (presence of lupus anticoagulant, IgG and/or IgM anticardiolipin and anti beta 2 glycoprotein I antibodies at >40 GPL or MPL units or > the 99th centile of normal*.

(*patients who have previously been triple aPL-positive and have single or double aPL positivity on at least 2 occasions over at least 6 months, including once within 1 month prior to randomisation, can be recruited to the trial)

2. Pregnant or lactating women

3. Severe renal impairment with creatinine clearance < 30 mL/min (i.e. 29 mL/min or less)

4. Liver function tests ALT > 3 x ULN

5. Cirrhotic patients with Child Pugh B or C

6. Thrombocytopenia (platelets < 75 x 109/L)

7. Non-adherence on warfarin (based on clinical assessment)

8. Patients taking strong inhibitors of both CYP3A4 and P-gp pathways such as

9. Systemic azole antifungals (e.g. ketoconazole, itraconazole, voriconazole, posaconazole)

10. Patients on human immunodeficiency virus (HIV) protease inhibitors (e.g. ritonavir)

11. Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)

12. Patients on dronedarone

13. Patients on levetiracetam, sodium valproate/valproic acid, oxcarbazepine or topiramate

14. Patients less than 18 years of age

15. Refusal to consent to the site informing General Practitioner (GP) and Healthcare Professional responsible for anticoagulation care of the participant.

16. Contraindications to MRI (e.g. cardiac pacemaker, severe claustrophobia, inability to lie flat: patients who do not meet local safety rules for MRI).

17. Patients at high risk of bleeding and not suitable for anticoagulation therapy.

18. Previous known allergy or intolerance to warfarin or rivaroxaban.

19. Women planning to become pregnant within the 2-year follow-up period.

20. Patients with known galactose intolerance, total lactase deficiency or galactose malabsorption.

21. Patients who have had active cancer (excluding non-melanoma skin cancers) within the last 2 years

22. Any other reason that the PI or delegate considers would make the patient unsuitable to enter RISAPS.