NCT02122718

Brief Summary

Recurrent stroke and cognitive decline are common after ischaemic stroke. Allopurinol, a drug usually used to treat gout, has been shown to reduce heart ischaemia, heart size, and arterial stiffness and to relax brain blood vessels and may reduce the blood pressure. All of these properties may be associated with a lower risk of second stroke and cognitive decline. We now aim to explore whether allopurinol will reduce further damage to the brain (called white matter hyper-intensities) after stroke and also whether it reduces heart size and blood pressure after stroke. We will conduct a multi-centre randomised, double-blind placebo controlled study to investigate whether two years allopurinol 300 mg twice per day (BD) improves these 3 outcomes, which are inextricably linked to risk of recurrence and cognitive decline after ischaemic stroke.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
464

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started May 2014

Longer than P75 for phase_4

Geographic Reach
1 country

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 23, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 24, 2014

Completed
7 days until next milestone

Study Start

First participant enrolled

May 1, 2014

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2021

Completed
Last Updated

November 12, 2021

Status Verified

November 1, 2021

Enrollment Period

6.8 years

First QC Date

April 23, 2014

Last Update Submit

November 11, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • White matter hyper-intensities (WMH) progression rate over 2 years, defined using the Rotterdam Progression Score

    2 years

Secondary Outcomes (18)

  • change in mean day-time systolic BP at 1 month

    1 month

  • change in mean day-time diastolic BP at 1 month

    1 month

  • Schmidt's Progression Score

    2 years

  • Fazekas score

    2 years

  • Scheltens scale score

    2 years

  • +13 more secondary outcomes

Other Outcomes (6)

  • Cardiac sub-study: Change in measured Left ventricular mass (LVM) at 2 years

    2 years

  • Cardiac sub-study: change in ejection fraction

    2 years

  • Cardiac Sub-study: change in end diastolic volume

    2 years

  • +3 more other outcomes

Study Arms (2)

Allopurinol

EXPERIMENTAL
Drug: Allopurinol

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

Allopurinol
Placebo

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Ischaemic Stroke/ Ischaemic lesion on brain imaging in relevant anatomical territory in patients with transient ischaemic attack.
  • Age greater than 50 years. -- Consent within one month of stroke.

You may not qualify if:

  • Modified Rankin scale score of 5 (at end of the possible enrolment window of one month after stroke).
  • Diagnosis of dementia (defined as a documented diagnosis or a screening Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.6 or more).
  • Cognitive impairment deemed sufficient to compromise capacity to consent or to comply with the protocol (in the opinion of the local investigator).
  • Dependent on daily help from others for basic or instrumental activities of daily living prior to stroke (defined as assistance needed with toileting, walking or dressing).
  • Significant co-morbidity or frailty likely to cause death within 24 months or likely to make adherence to study protocol difficult for participant (in the opinion of the local investigator).
  • Contra-indication to or indication for administration of allopurinol (as detailed in Summary of Product Characteristics on the XILO-FIST web portal and in trial master file).
  • Concurrent azathioprine, 6-mercaptopurine therapy, other cytotoxic therapies, cyclosporin, theophylline and didanosine.
  • Significant hepatic impairment (defined as serum bilirubin, Aspartate Aminotransferase (AST) or Alanine transaminase (ALT) greater than three times upper limit of normal (ULN)).
  • Estimated Glomerular Filtration Rate \< 30 mls/min
  • Contraindication to MRI scanning.
  • Women who are pregnant or breastfeeding.
  • Women of childbearing potential who are unable or unwilling to use contraception.
  • Prisoners.
  • Active participation in another Clinical Trial of Investigational Medicinal Product (CTIMP) or device trial or participation within the past month.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Altnagelvin Campus

Londonderry, County Derry, BT47 6SB, United Kingdom

Location

Broomfield Hospital

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Southend University Hospital

Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

Location

Darent Valley Hospital

Dartford, Kent, DA2 8DA, United Kingdom

Location

The Royal London Hospital

Whitechapel, London, E1 1BB, United Kingdom

Location

Northumbria NHS Trust

Ashington, Northumberland, NE63 9JJ, United Kingdom

Location

Royal United Hospital

Bath, Somerset, BA1 3NG, United Kingdom

Location

Royal Stoke University Hosptial

Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom

Location

NHS Grampian

Aberdeen, AB25 2ZD, United Kingdom

Location

NHS Lanarkshire

Airdrie, ML6 0JS, United Kingdom

Location

NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

South West Acute Hospital

Enniskillen, BT74 6DN, United Kingdom

Location

NHS Greater Glagsow and Clyde

Glasgow, G11 6NT, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Barnet Hospital

London, EN5 3DJ, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

UCL Stroke Research Centre

London, WC1B 5EH, United Kingdom

Location

Luton and Dunstable University Hosptial

Luton, LU4 0DZ, United Kingdom

Location

Newcastle UPon Tyne Hospitals NHS Trust

Newcastle, NE2 4AB, United Kingdom

Location

Nottingham University

Nottingham, NG5 1PB, United Kingdom

Location

City Hospital Sunderland NHS Foundation Trust

Sunderland, SR4 7TP, United Kingdom

Location

Related Publications (2)

  • Dawson J, Robertson M, Dickie DA, Bath P, Forbes K, Quinn T, Broomfield NM, Dani K, Doney A, Houston G, Lees KR, Muir KW, Struthers A, Walters M, Barber M, Bhalla A, Cameron A, Dyker A, Guyler P, Hassan A, Kearney MT, Keegan B, Lakshmanan S, Macleod MJ, Randall M, Shaw L, Subramanian G, Werring D, McConnachie A. 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. 2023 Feb 16;57:101863. doi: 10.1016/j.eclinm.2023.101863. eCollection 2023 Mar.

  • Dawson J, Broomfield N, Dani K, Dickie DA, Doney A, Forbes K, Houston G, Kean S, Lees K, McConnachie A, Muir KW, Quinn T, Struthers A, Walters M. Xanthine oxidase inhibition for the improvement of long-term outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST) - Protocol for a randomised double blind placebo-controlled clinical trial. Eur Stroke J. 2018 Sep;3(3):281-290. doi: 10.1177/2396987318771426. Epub 2018 Apr 18.

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

PurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Jesse Dawson

    University of Glasgow

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 23, 2014

First Posted

April 24, 2014

Study Start

May 1, 2014

Primary Completion

February 1, 2021

Study Completion

February 1, 2021

Last Updated

November 12, 2021

Record last verified: 2021-11

Locations