RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Rivaroxaban Versus Warfarin for Stroke Patients With Antiphospholipid Syndrome, With or Without SLE (RISAPS): a Randomised, Controlled, Open label, Phase II/III, Non-inferiority Trial.

140 patients will be randomised with a ratio of 1:1 to receive either:

• Rivaroxaban 15mg twice daily orally for 24 months or

• Warfarin (standard of care in the RISAPS trial) to maintain a target INR of 3.5 (range 3.0-4.0) for 24 months.

The primary outcome of the trial is the rate of change in brain white matter hyperintensity (WMH) volume between baseline and 24 months follow up, assessed on brain magnetic resonance imaging (MRI), a surrogate marker of ischaemic damage.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Collaborators: Arthritis Research UK; Barking, Havering and Redbridge University Hospitals NHS Trust; Barts & The London NHS Trust; Guy's and St Thomas' NHS Foundation Trust; Hammersmith Hospitals NHS Trust; King's College Hospital NHS Trust; King's College London; Manchester University NHS Foundation Trust; St George's University Hospitals NHS Foundation Trust; University College London Hospitals
• Treatments: Rivaroxaban; Warfarin

Criteria

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.

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

Exclusion Criteria

1. Pregnant or lactating women

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

3. Liver function tests ALT > 3 x ULN

4. Cirrhotic patients with Child Pugh B or C

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

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

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

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

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

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

9. Patients on dronedarone

10. Patients less than 18 years of age

11. Refusal to consent to the site informing General Practitioner and Healthcare Professional responsible for anticoagulation care of the participant

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

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

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

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

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

17. Any other reason that the PI considers would make the patient unsuitable to enter RISAPS.