Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial

Jesse Dawson* (Corresponding Author), Michele Robertson, David Alexander Dickie, Phillip Bath, Kirsten Forbes, Terence Quinn, Niall M. Broomfield, Krishna Dani, Alex Doney, Graeme Houston, Kennedy R. Lees, Keith W. Muir, Allan Struthers, Matthew Walters, Mark Barber, Ajay Bhalla, Alan Cameron, Alexander Dyker, Paul Guyler, Ahamad HassanMark T. Kearney, Breffni Keegan, Sekaran Lakshmanan, Mary Joan Macleod, Marc Randall, Louise Shaw, Ganesh Subramanian, David Werring, Alex McConnachie

*Corresponding author for this work

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Summary Background People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). Methods In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. Findings Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference −0.17, 95% CI −0.52 to 0.17, p = 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. Interpretation Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. Funding The British Heart Foundation and the UK Stroke Association.
Original languageEnglish
Article number101863
Number of pages10
Early online date16 Feb 2023
Publication statusPublished - 1 Mar 2023

Bibliographical note

This work was supported by the Stroke Association and British Heart Foundation [grant number TSA BHF 2013/01]. The work of Dr David Dickie and Dr Terry Quinn is funded by the Stroke Association. We would like to thank Christine McAlpine, Ruth Graham, Glasgow Royal Infirmary, UK; Lauren Pearce, Royal United Hospital, UK; Caroline Fornolles, Louise Tate, Frances Justin, Luton and Dunstable University Hospital, UK; Dean Waugh, Leeds Teaching Hospitals NHS Trust, UK; Donal Concannon, Altnagelvin Hospital, UK; Sharon Tysoe, Nina Francia, Nisha Menon, Raji Prabakaran, Southend University Hospital, UK; Amy Ashton, Caroline Watchurst, Marilena Marinescu, Sabaa Obarey, Scheherazade Feerick, University College London NHS Foundation Trust, UK; and Janice Irvine, Sandra Williams, and German Guzman Gutierrez, Aberdeen Royal Infirmary, UK; Caroline Fox and Joanne Topliffe, Broomfield Hospital, Essex, UK.

Data Availability Statement

Data sharing statement
Study data, including brain MRI will be shared with the Virtual International Stroke Trials Archive after publication of the primary manuscript. Study data including anonymized individual level participant data will be shared with academic investigators or health care professionals following review and approval of a proposal and subject to a data sharing agreement (contact jesse.dawson@glasgow.ac.uk).


  • Stroke
  • Allopurinol
  • Hypertension
  • White matter hyperintensities


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