RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome

NCT ID: NCT03684564

Last Updated: 2023-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-09

Study Completion Date

2025-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Antiphospholipid Syndrome Systemic Lupus Erythematosus Stroke Ischemic Stroke Brain Ischemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Rivaroxaban (Treatment Arm)

Group Type EXPERIMENTAL

Rivaroxaban

Intervention Type DRUG

Oral tablet 15 mg twice daily for 24 months

Warfarin (Control Arm)

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Rivaroxaban

Oral tablet 15 mg twice daily for 24 months

Intervention Type DRUG

Warfarin

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Exclusion Criteria

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


1. 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)
2. Pregnant or lactating women
3. Severe renal impairment with creatinine clearance \< 30 mL/min (i.e. 29 mL/min or less)
4. Liver function tests ALT \> 3 x ULN
5. Cirrhotic patients with Child Pugh B or C
6. Thrombocytopenia (platelets \< 75 x 109/L)
7. Non-adherence on warfarin (based on clinical assessment)
8. 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)
9. Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)
10. Patients on dronedarone
11. Patients on levetiracetam, sodium valproate/valproic acid, oxcarbazepine or topiramate
12. Patients less than 18 years of age
13. Refusal to consent to the site informing General Practitioner (GP) and Healthcare Professional responsible for anticoagulation care of the participant.
14. Contraindications to MRI (e.g. cardiac pacemaker, severe claustrophobia, inability to lie flat: patients who do not meet local safety rules for MRI).
15. Patients at high risk of bleeding and not suitable for anticoagulation therapy.
16. Previous known allergy or intolerance to warfarin or rivaroxaban.
17. Women planning to become pregnant within the 2-year follow-up period.
18. Patients with known galactose intolerance, total lactase deficiency or galactose malabsorption.
19. Patients who have had active cancer (excluding non-melanoma skin cancers) within the last 2 years
20. Any other reason that the PI or delegate considers would make the patient unsuitable to enter RISAPS.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University College London Hospitals

OTHER

Sponsor Role collaborator

Barking, Havering and Redbridge University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Hammersmith Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Epsom and St Helier University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Barts & The London NHS Trust

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

Versus Arthritis (Funder)

UNKNOWN

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Hannah Cohen

Role: PRINCIPAL_INVESTIGATOR

University College London Hospitals NHS Foundation Trust/University College London

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Epsom and St Helier University Hospitals NHS Trust

Epsom, , United Kingdom

Site Status

Barts and the London Hospitals, Barts Health NHS Trust

London, , United Kingdom

Site Status

Hammersmith Hospital, Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Kings College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

University College Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

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

Romford, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CTU/2015/174

Identifier Type: -

Identifier Source: org_study_id