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

Dawson, J. et al. (2023) 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. EClinicalMedicine, 57, 101863. (doi: 10.1016/j.eclinm.2023.101863) (PMID:36864979) (PMCID:PMC9972492)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McConnachie, Professor Alex and Lees, Professor Kennedy and Barber, Dr Mark and Dickie, Dr David Alexander and Robertson, Mrs Michele and Quinn, Professor Terry and Cameron, Dr Alan and Dawson, Professor Jesse and Broomfield, Dr Niall and Dani, Dr Krishna and Muir, Professor Keith and Walters, Professor Matthew
• Authors: Dawson, J., Robertson, M., Dickie, D. A., Bath, P., Forbes, K., Quinn, T., Broomfield, N. M., Dani, K., Doney, A., Houston, G., Lees, K. R., Muir, K. W., Struthers, A., Walters, M., Barber, M., Bhalla, A., Cameron, A., Dyker, A., Guyler, P., Hassan, A., Kearney, M. T., Keegan, B., Lakshmanan, S., Macleod, M. J., Randall, M., Shaw, L., Subramanian, G., Werring, D., and McConnachie, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: EClinicalMedicine
• Publisher: Lancet Publishing Group
• ISSN: 2589-5370
• ISSN (Online): 2589-5370
• Published Online: 16 February 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in EClinicalMedicine 57: 101863
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190716		Xanthine oxidase inhibition for improvement of Long-term Outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST)	Jesse Dawson	Stroke Association (STROKEAS)	TSA BHF 2013/01	Institute of Cardiovascular & Medical Sciences