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Antiphospholipid SyndromePhase 2RISAPSNCT03684564

RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome

A Phase 2 study testing Rivaroxaban and Warfarin in people with Antiphospholipid Syndrome and Systemic Lupus Erythematosus, run by University College, London at 6 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rivaroxaban and Warfarin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
6 sitesUnited Kingdom
Study dates
9 Jul 2021to 31 Jul 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 23Show fewer
  • 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)
  • Patients on dronedarone
  • Patients on levetiracetam, sodium valproate/valproic acid, oxcarbazepine or topiramate
  • Patients less than 18 years of age
  • Refusal to consent to the site informing General Practitioner (GP) and Healthcare Professional responsible for anticoagulation care of the participant.
  • 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.
  • Previous known allergy or intolerance to warfarin or rivaroxaban.
  • Women planning to become pregnant within the 2-year follow-up period.
  • Patients with known galactose intolerance, total lactase deficiency or galactose malabsorption.
  • Patients who have had active cancer (excluding non-melanoma skin cancers) within the last 2 years
  • Any other reason that the PI or delegate considers would make the patient unsuitable to enter RISAPS.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United Kingdom6 sites

  • Epsom and St Helier University Hospitals NHS Trust

    Epsom

  • Barts and the London Hospitals, Barts Health NHS Trust

    London

  • Hammersmith Hospital, Imperial College Healthcare NHS Trust

    London

  • Kings College Hospital NHS Foundation Trust

    London

  • University College Hospitals NHS Foundation Trust

    London

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

    Romford

Other trials in United Kingdom

About this study

Official title: 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.

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.

Read the 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.

Being tested
Rivaroxaban, Warfarin
Medical subject headings
Antiphospholipid Syndrome, Lupus Erythematosus, Systemic, Stroke, Ischemic Stroke, Brain Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RivaroxabanDrug

    Oral tablet 15 mg twice daily for 24 months

  • WarfarinDrug

    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

Study groups in NCT03684564
Study groupRoleWhat they receive
Rivaroxaban (Treatment Arm)ExperimentalNot described
Receives: Drug: Rivaroxaban
Warfarin (Control Arm)Active comparatorNot described
Receives: Drug: Warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (6)

  1. A) Efficacy - Neuroradiological markers

    1. 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
    2. cortical or subcortical
    3. assessment of volume iv) Cerebral venous occlusions

    Measured: 24 months

  2. Clinical

    (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 score

    Measured: 24 months

  3. B) Safety

    (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.

    Measured: 24 months

  4. C) Health Economics

    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.

    Measured: 24 months

  5. D) Anticoagulation intensity

    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

    Measured: 24 months

  6. ii) Changes in total brain volume, white matter volume and grey matter volume on T1w volumetric images on MRI

    This will be used as a marker for neurological efficacy of the IMP compared with current standard of care.

    Measured: 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2018
  2. Study start9 Jul 2021
  3. Primary completion31 Jul 2025
  4. Study completion31 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03684564
Sponsor's protocol ID
CTU/2015/174
Acronym
RISAPS
Status last verified
May 2026
First submitted
13 Aug 2018
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rivaroxaban and Warfarin in people with Antiphospholipid Syndrome and Systemic Lupus Erythematosus, run by University College, London at 6 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03684564.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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