RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome
- Conditions
- Antiphospholipid SyndromeSystemic Lupus ErythematosusStrokeBrain IschemiaIschemic Stroke
- Interventions
- Registration Number
- NCT03684564
- Lead Sponsor
- University College, London
- 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.
- Detailed Description
The RISAPS trial follows on from the RAPS (Rivaroxaban in Antiphospholipid Syndrome) study that showed that rivaroxaban could offer a potentially effective alternative to warfarin for patients with antiphospholipid syndrome (APS) who have thrombosis (blood clots) in their veins, rather than in their arteries and require standard intensity anticoagulation (blood thinning).
Currently, APS patients who have had an ischaemic stroke (which occurs when blood flow to an area of brain is cut off) are treated with warfarin to reduce the risk of a recurrence. Warfarin tends to have a variable 'blood thinning' effect in patients with APS, necessitating frequent (usually weekly) INR blood tests to monitor the effect of the warfarin, which is inconvenient for patients.
The RISAPS trial will compare higher intensity (higher dose) rivaroxaban versus higher intensity warfarin (current standard of care treatment) for 24 months, in APS patients, with or without lupus (systemic lupus erythematosus; SLE), requiring higher intensity anticoagulation after experiencing a stroke, a 'mini stroke' (also known as a transient ischaemic attack) or other ischaemic brain damage (caused by blood clots in the brain arteries or smaller blood vessels). When compared with warfarin, a dvantages of rivaroxaban include, fixed dose prescribing and no need for monitoring of anticoagulant effect.
Furthermore, rivaroxaban has fewer drug-food interactions, and significantly fewer drug-drug interactions than warfarin. If rivaroxaban is no worse than warfarin for anticoagulation of APS patients with stroke or other ischaemic brain manifestations, it could become the standard of care for the treatment of APS patients, with or without lupus, who have experienced stroke or other ischaemic brain manifestations and improve patients' quality of life.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 43
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rivaroxaban (Treatment Arm) Rivaroxaban - Warfarin (Control Arm) Warfarin -
- Primary Outcome Measures
Name Time Method 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. 24 months 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.
- Secondary Outcome Measures
Name Time Method ii) Changes in total brain volume, white matter volume and grey matter volume on T1w volumetric images on MRI 24 Months This will be used as a marker for neurological efficacy of the IMP compared with current standard of care.
Clinical 24 months (i) Vascular events
1. Ischaemic stroke or transient ischaemic attack
2. Occlusive arterial events in other sites including systemic embolism
3. Cerebral venous thrombosis
4. Venous thromboembolism in other sites
5. Microvascular thrombosis
6. Superficial venous thrombosis
The following events defined and reported according to CTCAE v5.
ii) Death
iii) Composite clinical outcomes
1. A composite of all thrombotic events: arterial, venous, microvascular and death.
2. Major adverse cardiac and cerebrovascular events (MACCE)
iv) Rate of change in cognitive function assessed by the Montreal Cognitive Assessment (MoCA) in conjunction with the Queen Square Cognitive Assessment scoreB) Safety 24 months (i) Bleeding: All bleeding events: major, clinically relevant non-major or minor (ii) Serious adverse events other than major bleeding (iii) Cerebral microbleeds (CMB) assessed with susceptibility-weighted imaging (SWI) as a surrogate marker of bleeding risk.
C) Health Economics 24 months 1. Quality of life (QoL) assessed using EQ-5D-5L
2. Health and social care resource use assessed using trial follow-up visit case report forms (CRFs)
3. Mean incremental cost per quality adjusted life year (QALY)
Serious adverse events other than major bleeding using the criteria within the CTCAE version 5.A) Efficacy - Neuroradiological markers 24 months i) Mean diffusivity and fractional anisotropy as a measure of microstructural white matter damage derived from diffusion tensor imaging (DTI) ii) Changes in total brain volume, white matter volume and grey matter volume on T1 weighted volumetric images iii) Brain infarcts
1. cortical or subcortical
2. assessment of volume iv) Cerebral venous occlusionsD) Anticoagulation intensity 24 months 1. Rivaroxaban i) Rivaroxaban anti-Xa levels
2. Warfarin i) Time in target therapeutic range (TTR) ii) Amidolytic factor X as a lupus anticoagulant independent assessment of warfarin anticoagulant effect
Trial Locations
- Locations (6)
Barts and the London Hospitals, Barts Health NHS Trust
🇬🇧London, United Kingdom
Hammersmith Hospital, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
University College Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Epsom and St Helier University Hospitals NHS Trust
🇬🇧Epsom, United Kingdom
Kings College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Queens Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust
🇬🇧Romford, United Kingdom