Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 5;8(5):102468.
doi: 10.1016/j.rpth.2024.102468. eCollection 2024 Jul.

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial

Prabal Mittal  1   2 , Rafael Gafoor  3 , Zara Sayar  1   4 , Maria Efthymiou  2 , Ibrahim Tohidi-Esfahani  1   2 , Stella Appiah-Cubi  5 , Deepa J Arachchillage  6   7 , David Atkinson  8 , Ekaterina Bordea  3 , M Jorge Cardoso  9 , Emilia Caverly  3 , Arvind Chandratheva  10   11 , Marisa Chau  3 , Nick Freemantle  3 , Carolyn Gates  1 , H Rolf Ja Ger  12 , Arvind Kaul  13 , Chris Mitchell  14 , Hanh Nguyen  3 , Bunis Packham  15 , Jaye Paskell  1 , Jignesh P Patel  16 , Chris Round  3 , Giovanni Sanna  17 , Abbas Zaidi  18 , David J Werring  10 , David Isenberg  19   20 , Hannah Cohen  1   2
Affiliations

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial

Prabal Mittal et al. Res Pract Thromb Haemost. .

Abstract

Background: Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation.

Objectives: The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations.

Methods: This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling.

Conclusion: Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials.

Keywords: antiphospholipid syndrome; ischemic stroke; rivaroxaban; thrombosis; warfarin.

PubMed Disclaimer

Figures

Figure
Figure
Overview of the trial schedule. APS, antiphospholipid syndrome; FBC, full blood count; INR, international normalized ratio; MARS, Medication Adherence Rating Scale; MRI, magnetic resonance imaging; QoL, quality of life; SLE, systemic lupus erythematosus.
See this image and copyright information in PMC

References

    1. World Health Organization The top 10 causes of death. http://www.who.int/mediacentre/factsheets/fs310/en/ ; 2020 [accessed October 11, 2023].
    1. Adamson J., Beswick A., Ebrahim S. Is stroke most common cause of disability? J Stroke Cerebrovasc Dis. 2004;13:171–177. - PubMed
    1. Gracia-Tello A., Jones C.R., Isenberg D D. Systemic Lupus erythematosus: detailed anatomy of a cohort (follow-up for more than 35 years) Arthritis Rheum. 2016;68(suppl 10)
    1. Ruiz-Irastorza G., Egurbide M.V., Ugalde J., Aguirre C. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med. 2004;164:77–82. - PubMed
    1. Riancho-Zarrabeitia L., Martínez-Taboada V., Rúa-Figueroa I., Alonso F., Galindo-Izquierdo M., Ovalles J., et al. Antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) implies a more severe disease with more damage accrual and higher mortality. Lupus. 2020;29:1556–1565. - PubMed

LinkOut - more resources