RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome

Prior treatment

• 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)
• Previous known allergy or intolerance to warfarin or rivaroxaban.

Other illness

• Patients taking strong inhibitors of both CYP3A4 and P-gp pathways such as
  • Systemic azole antifungals (e.g. ketoconazole, itraconazole, voriconazole, posaconazole)
  • Patients on human immunodeficiency virus (HIV) protease inhibitors (e.g. ritonavir)
• Contraindications to MRI (e.g. cardiac pacemaker, severe claustrophobia, inability to lie flat: patients who do not meet local safety rules for MRI).
• Patients at high risk of bleeding and not suitable for anticoagulation therapy.
• Patients who have had active cancer (excluding non-melanoma skin cancers) within the last 2 years

Lab values

• Severe renal impairment with creatinine clearance \< 30 mL/min (i.e. 29 mL/min or less)
• Liver function tests ALT \> 3 x ULN
• Thrombocytopenia (platelets \< 75 x 109/L)
• Patients on levetiracetam, sodium valproate/valproic acid, oxcarbazepine or topiramate

Age

• Patients less than 18 years of age

Other

• Pregnant or lactating women
• Cirrhotic patients with Child Pugh B or C
• Non-adherence on warfarin (based on clinical assessment)
• Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)
• Patients on dronedarone
• Refusal to consent to the site informing General Practitioner (GP) and Healthcare Professional responsible for anticoagulation care of the participant.
• Women planning to become pregnant within the 2-year follow-up period.
• Patients with known galactose intolerance, total lactase deficiency or galactose malabsorption.
• Any other reason that the PI or delegate considers would make the patient unsuitable to enter RISAPS.

• 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.
• 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).
• Patients must weigh ≥ 50kg and ≤ 135kg.
• Women must be on adequate contraception, barrier or hormonal, unless postmenopausal or sterilised.