Rationale and design of the AXIOMATIC-SSP phase II trial: Antithrombotic treatment with factor XIa inhibition to Optimize Management of Acute Thromboembolic events for Secondary Stroke Prevention

Mukul Sharma, Carlos A. Molina, Kazunori Toyoda, Daniel Bereczki, Scott E. Kasner, Helmi L. Lutsep, Georgios Tsivgoulis, George Ntaios, Anna Czlonkowska, Ashfaq Shuaib, Pierre Amarenco, Matthias Endres, Hans Christoph Diener, David Gailani, Anja Kahl, Mark Donovan, Vidya Perera, Danshi Li, Graeme J. Hankey

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Individuals with ischemic stroke or transient ischemic attack (TIA) have a high early risk of ischemic stroke despite dual antiplatelet therapy. The risk of ischemic stroke, and associated disability, represents a significant unmet clinical need. Genetic variants resulting in reduced factor XI levels are associated with reduced risk for ischemic stroke but are not associated with increased intracranial bleeding. Milvexian is an oral small-molecule inhibitor of FXIa that binds activated factor XI with high affinity and selectivity and may reduce the risk of stroke when added to antiplatelet drugs without significant bleeding. We aimed to evaluate the dose-response relationship of milvexian in participants treated with dual antiplatelets. Methods: We began a phase II, double-blinded, randomized, placebo-controlled trial at 367 sites in 2019. Participants (N = 2366) with ischemic stroke (National Institutes of Health Stroke Scale score ≤7) or high-risk TIA (ABCD2 score ≥6) were randomized to 1 of 5 doses of milvexian or placebo for 90 days. Participants also received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg for 90 days. The efficacy endpoint was the composite of ischemic stroke or incident infarct on magnetic resonance imaging. Major bleeding, defined as type 3 or 5 bleeding according to the Bleeding Academic Research Consortium, was the safety endpoint. Participant follow-up will end in 2022. Conclusion: The AXIOMATIC-SSP trial will evaluate the dose-response of milvexian for ischemic stroke occurrence in participants with ischemic stroke or TIA.

Original languageEnglish (US)
Article number106742
JournalJournal of Stroke and Cerebrovascular Diseases
Volume31
Issue number10
DOIs
StatePublished - Oct 2022

Keywords

  • Factor XI
  • MRI
  • Milvexian
  • Randomized trial
  • Stroke
  • Stroke prevention

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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