Xanthine Oxidase Inhibition for Improvement of Long-term Outcomes Following Ischaemic Stroke and Transient Ischaemic Attack (XILO-FIST)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by NHS Greater Glasgow and Clyde
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier:
NCT02122718
First received: April 23, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Ischaemic Stroke
Drug: Allopurinol
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Xanthine Oxidase Inhibition for Improvement of Long-term Outcomes Following Ischaemic Stroke and Transient Ischaemic Attack

Resource links provided by NLM:


Further study details as provided by NHS Greater Glasgow and Clyde:

Primary Outcome Measures:
  • White matter hyper-intensities (WMH) progression rate over 2 years, defined using the Rotterdam Progression Score [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • change in mean day-time systolic BP at 1 month [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • change in mean day-time diastolic BP at 1 month [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Schmidt's Progression Score [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Fazekas score [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Scheltens scale score [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • New brain infarction on MRI [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Rotterdam Progression Score with those who die / become too frail to undergo MRI being assigned the highest score [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Montreal Cognitive Assessment (MoCA) score [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incident dementia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • change in mean day-time systolic BP at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • change in mean day-time diastolic BP at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • blood pressure variability [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Quality of life (EQ-5D, Stroke Specific Quality of Life Scale (SS-QOL)) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Recurrent stroke [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Recurrent myocardial infarction (MI), stroke or cardiac death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incident atrial fibrillation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinic blood pressure [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Cardiac sub-study: Change in measured Left ventricular mass (LVM) at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cardiac sub-study: change in ejection fraction [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cardiac Sub-study: change in end diastolic volume [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cardiac sub-study: change in end systolic volume [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cardiac Sub-study: change in stroke volume [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cardiac sub-study: change in left atrial diameter [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 464
Study Start Date: May 2014
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allopurinol Drug: Allopurinol
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02122718

Contacts
Contact: Jesse Dawson, MD, BSc (hon), MBChB (hons), 0141 2116395 jesse.dawson@glasgow.ac.uk
Contact: Pamela MacKenzie 01412112176 Pamela.MacKenzie@glasgow.ac.uk

Locations
United Kingdom
NHS Tayside Not yet recruiting
Dundee, United Kingdom, DD1 9SY
Contact: Allan Struthers         
NHS Greater Glagsow and Clyde Not yet recruiting
Glasgow, United Kingdom, G11 6NT
Contact: Jesse Dawson         
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
Investigators
Principal Investigator: Jesse Dawson University of Glasgow
  More Information

No publications provided

Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT02122718     History of Changes
Other Study ID Numbers: GN12MT494, TSA BHF 2013/01
Study First Received: April 23, 2014
Last Updated: April 23, 2014
Health Authority: United Kingdom: National Health Service

Additional relevant MeSH terms:
Ischemic Attack, Transient
Ischemia
Stroke
Cerebral Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Allopurinol
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014