Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome (RISAPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03684564
Recruitment Status : Not yet recruiting
First Posted : September 25, 2018
Last Update Posted : September 25, 2018
Sponsor:
Collaborators:
Arthritis Research UK
King's College London
University College London Hospitals
Hammersmith Hospitals NHS Trust
Guy's and St Thomas' NHS Foundation Trust
Barts & The London NHS Trust
King's College Hospital NHS Trust
Information provided by (Responsible Party):
University College, London

Brief Summary:

RISAPS: Rivaroxaban versus warfarin for stroke patients with antiphospholipid syndrome, with or without SLE: a randomised, controlled, phase II/III, non-inferiority trial

140 patients will be randomised at a 1:1 to receive either

  • rivaroxaban 15mg twice daily orally for 24 months or
  • warfarin (as per standard care) to maintain a target INR of 3.5 (range 3.0-4.0) The primary outcome for the trial is the rate of change in brain white matter hyoerintensity (WMH) volume on MRI, a surrogate marker of ischaemic damage, assessed on the 3D FLAIR sequence, between baseline and 24 months follow up.

Condition or disease Intervention/treatment Phase
Antiphospholipid Syndrome Drug: Rivaroxaban Drug: Warfarin Phase 2 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: Rivaroxaban
rivaroxaban 15 mg twice daily orally for 24 months
Drug: Rivaroxaban
rivaroxaban oral tablet twice daily for 24 months

Active Comparator: Warfarin (Standard of Care)
warfarin (as per standard of care) to maintain a target INR of 3.5 (range 3.0-4.0) for 24 months
Drug: Warfarin
warfarin (standard of care) to maintain a target INR of 3.5 (range 3.0 to 4.0)




Primary Outcome Measures :
  1. To compare the efficacy of high intensity oral rivaroxaban vs high intensity warfarin in patients with antiphospholipid syndrome with or without systemic lupus erythematosus who have had a stroke or other ischaemic brain manifestations. [ Time Frame: 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 :
  1. Health Economics Analysis- cost per adjusted life year [ Time Frame: 24 months ]
    Mean incremental cost per quality adjusted life year (QALY) using responses on the five-level EQ-5D-5L completed at baseline and each follow-up visit.

  2. Clinical Measures of Efficacy- Vascular events [ Time Frame: 24 months ]

    The following events defined and reported according to CTCAE v5

    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

  3. Clinical Measures of Efficacy- Death [ Time Frame: 24 months ]
    All reported deaths will be entered into the statistical model irrespective of the cause of death.

  4. A composite outcome measure of thrombotic events, including arterial, venous micro vascular and death. [ Time Frame: 24 months ]
    A composite outcome compiled of all reported thrombotic events and deaths during the trial as AEs or SAEs. All AEs & SAEs during the trial will be categorised using the CTCAE v5.

  5. Safety Events- bleeding all bleeds [ Time Frame: 24 months ]
    Bleeding: All bleeding events: major , clinically relevant or non-major , minor using the trial definitions for bleeding events

  6. Safety - All Serious Adverse Events [ Time Frame: 24 months ]
    Serious adverse events other than major bleeding using the criteria within the CTCAE version 5

  7. Safety- Cerebral Micro bleeds [ Time Frame: 24 months ]
    Cerebral microbleeds (CMB) assessed with susceptibility-weighted (SWI) imaging as a surrogate marker of bleeding risk

  8. Anti-coagulation intensity- Rivaroxaban anti-Xa levels [ Time Frame: 24 months ]
    Rivaroxaban anti-Xa levels

  9. Anti-coagulation intensity-Warfarin [ Time Frame: 24 months ]
    i) Time in target therapeutic range (TTR) ii) Amidolytic factor X as a lupus anticoagulant independent assessment of warfarin anticoagulant effect

  10. ii) Changes in total brain volume, white matter volume and grey matter volume on T1w volumetric images on MRI [ Time Frame: 24 Months ]
    This will be used as a marker for neurological efficacy of the IMP compared with current standard of care.

  11. Composite of clinical cardiac and cerebrovascular outcomes using MACCE [ Time Frame: 24 Months ]
    This will be a composite outcome analysis of all the cardiac and cerebrovascular events defined using MACCE reported on the trial



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be confirmed as having persistent antiphospholipid antibodies (aPL)*.
  2. One or more of: a) Ischaemic stroke; b) transient ischaemic attack (TIA) (one or more episodes) with evidence of ischaemic injury on brain magnetic resonance imaging (MRI) 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.
  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 creatinine clearance (Cockcroft & Gault: Appendix 2) <30 mL/min (i.e. 29 mL/min or less)
  3. Liver function tests ALT > 2 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 on azole antifungals (e.g. ketoconazole, itraconazole)
  8. Patients on 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 less than 18 years of age
  12. Refusal to consent to the site informing GP and healthcare professional responsible for anticoagulation care, of participation
  13. Contraindications to MRI (e.g. cardiac pacemaker, severe claustrophobia, inability to lie flat: patients who do not meet local safety rules for MRI).
  14. Patients at high risk of bleeding and not suitable for anti-coagulation therapy.
  15. Previous known allergy or intolerance to warfarin or rivaroxaban.
  16. Women planning to become pregnant within the 2 year follow-up period.
  17. Patients with a known galactose intolerance, total lactase deficiency or galactose malabsorption.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03684564


Contacts
Layout table for location contacts
Contact: RISAPS Trial Manager 020 7907 4674 risaps@ucl.ac.uk

Sponsors and Collaborators
University College, London
Arthritis Research UK
King's College London
University College London Hospitals
Hammersmith Hospitals NHS Trust
Guy's and St Thomas' NHS Foundation Trust
Barts & The London NHS Trust
King's College Hospital NHS Trust
Investigators
Layout table for investigator information
Principal Investigator: Hannah Cohen UCLH

Layout table for additonal information
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT03684564     History of Changes
Other Study ID Numbers: CTU/2015/174
First Posted: September 25, 2018    Key Record Dates
Last Update Posted: September 25, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Antiphospholipid Syndrome
Syndrome
Disease
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Warfarin
Rivaroxaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action