RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome

NCT03684564 | Unknown Phase 2 DMC

• 1 other identifier: CTU/2015/174
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

Brief Summary

Rivaroxaban versus warfarin for stroke patients with antiphospholipid syndrome, with or without SLE (RISAPS): a randomised, controlled, open-label, phase IIb, non-inferiority proof of principle trial. 40 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.

Conditions

Antiphospholipid Syndrome; Systemic Lupus Erythematosus; Stroke; Ischemic Stroke; Brain Ischemia

Outcome Measures

Primary Outcomes (1)

• To compare the efficacy of high-intensity oral rivaroxaban (15mg twice daily) vs high-intensity warfarin, target INR 3.5 (range 3.0-4.0), in patients with APS with or without SLE who have had a stroke or other ischaemic brain manifestations.

  The comparison of efficacy will be based on the rate of change in brain white matter hyperintensity (WMH) volume on MRI, a surrogate marker of ischaemic damage, between baseline and 24 months follow up.

  24 months

Secondary Outcomes (6)

• A) Efficacy - Neuroradiological markers

  24 months

• Clinical

  24 months

• B) Safety

  24 months

• C) Health Economics

  24 months

• D) Anticoagulation intensity

  24 months

Other Outcomes (1)

• E. Exploratory Outcomes

  24 months

Study Arms (2)

Rivaroxaban (Treatment Arm)

EXPERIMENTAL

Drug: Rivaroxaban

Warfarin (Control Arm)

ACTIVE COMPARATOR

Drug: Warfarin

Interventions

Rivaroxaban DRUG

Oral tablet 15 mg twice daily for 24 months

Rivaroxaban (Treatment Arm)

Warfarin DRUG

Oral anticoagulant given as standard of care in the RISAPS trial to maintain a target INR of 3.5 (range 3.0-4.0) for 24 months

Warfarin (Control Arm)

Eligibility Criteria

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

You may not qualify if:

• 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.
• 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)
• Pregnant or lactating women
• Severe renal impairment with creatinine clearance \< 30 mL/min (i.e. 29 mL/min or less)
• Liver function tests ALT \> 3 x ULN
• Cirrhotic patients with Child Pugh B or C
• Thrombocytopenia (platelets \< 75 x 109/L)
• Non-adherence on warfarin (based on clinical assessment)
• 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)
• Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)

Sponsors & Collaborators

• University College, London: lead
• University College London Hospitals: collaborator
• Barking, Havering and Redbridge University Hospitals NHS Trust: collaborator
• Hammersmith Hospitals NHS Trust: collaborator
• Epsom and St Helier University Hospitals NHS Trust: collaborator
• Barts & The London NHS Trust: collaborator
• King's College Hospital NHS Trust: collaborator
• Versus Arthritis (Funder): collaborator

Study Sites (6)

Epsom and St Helier University Hospitals NHS Trust

Epsom, United Kingdom

Location

Barts and the London Hospitals, Barts Health NHS Trust

London, United Kingdom

Location

Hammersmith Hospital, Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, United Kingdom

Location

University College Hospitals NHS Foundation Trust

London, United Kingdom

Location

Queens Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust

Romford, United Kingdom

Location

MeSH Terms

Conditions

Antiphospholipid Syndrome; Lupus Erythematosus, Systemic; Stroke; Ischemic Stroke; Brain Ischemia

Interventions

Rivaroxaban; Warfarin

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hannah Cohen

  University College London Hospitals NHS Foundation Trust/University College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants enrolled in RISAPS will be randomly allocated 1:1 to receive either oral rivaroxaban 15mg twice daily or oral warfarin (standard of care in the RISAPS trial) to maintain a target INR of 3.5 (range 3.0-4.0) for 24 months.

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: September 25, 2018
• Study Start: July 9, 2021
• Primary Completion: February 1, 2025
• Study Completion: August 1, 2025
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)