Clinical syndrome of cortical or large subcortical stroke or TIA (TACS, PACS or cerebellar POCS) Circulatory System
Conditions
Interventions
IMP is defined by the active substance only, so any brand of isosorbide mononitrate (ISMN) and cilostazol that are available in the hospital pharmacy may be used.
All patients: Participants will be
patients who develop a contraindication to one of the drugs during the trial may continue taking the other drug.
Comparator: None (PROBE design).
Standard of care: UK guideline-based stroke prophy
Sponsors
University of Nottingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult, age >50 years, with no upper limit. 2. Clinical syndrome of cortical or large subcortical stroke or TIA (TACS, PACS or cerebellar POCS). 3. At least 7 days after the index event. 4. Stable medically according to the PI. 5. Has completed any phase of dual antiplatelet therapy. 6. Independent functionally or requires only limited help (mRS 0-3). 7. Able to swallow or has established enteral feeding route. 8. Brain imaging (CT or MRI scan) at the time of the index stroke/TIA shows moderate-severe white matter hyperintensities, Fazekas Score periventricular and deep =2. 9. The relevant radiology report will be uploaded as part of eligibility and assessed for these criteria. 10. Patient has capacity to give consent in the opinion of the PI or any delegated member of the research team; OR Patient lacks capacity and a legal representative is available to give proxy consent. 11. Likely to be available for follow-up at 6 months. 12. Women of childbearing potential and men with partners of childbearing potential must be willing to use contraception, provided they have the capacity.
Exclusion criteria
Exclusion criteria: 1. Lacunar infarct (LACS; so is eligible for LACI-3 trial). 2. Brain stem-only posterior circulation stroke syndrome (POCS). Note: cerebellar POCS are eligible. 3. Known monogenic cerebral small vessel disease. 4. Index event was an intracranial haemorrhage. Note: a past history of ICH before the index event is eligible. 5. Other active brain disease, e.g. brain tumour, multiple sclerosis, Parkinson’s disease, recurrent seizures, neurodevelopmental disorder. Note: well-controlled epilepsy present prior to the stroke, a single seizure at onset of the stroke, or provoked seizure, is not an exclusion. 6. Clinical diagnosis of dementia, e.g. letter from a memory clinic and/or taking acetylcholinesterase inhibitor or memantine. 7. Contraindication to both trial drugs 8. Indication for both trial drugs. Planned surgery during the trial period including carotid endarterectomy. Note: Patient becomes eligible after planned surgery. 'Prior and apparently successful carotid endarterectomy (or other surgery) is not an exclusion criterion and patients who would otherwise be eligible but require endarterectomy first may be randomised after recovery from successful endarterectomy 9. Diagnosis of hypotension, defined as sitting systolic blood pressure less than 100 mmHg. 10. History of drug overdose or attempted suicide. 11. Person is a visitor to the hospital’s region so cannot be followed, e.g. on holiday/from overseas. 12. Unlikely to comply with study procedures and follow-up procedures for whatever reason (e.g. history of poor medication compliance) in the opinion of the randomising physician. 13. Pregnancy, breastfeeding, or of child-bearing potential (a negative pregnancy test is needed prior to enrolment) and not using highly effective contraception. 14. Known renal impairment (most recent creatinine clearance 3 times upper limit normal). 16. Previously enrolled in CVD-Cog. 17. Enrolled in a study that does not have an agreement with CVD-Cog allowing co-enrolment (see up-to-date list of trials allowing co-enrolment on CVD-Cog website). 18. Women of childbearing potential and men with partners of childbearing potential who lack capacity 19. Cilostazol exclusion criteria - still allows randomisation to ISMN: 20. Definite indication for cilostazol: i.e. already prescribed. 21. Definite contraindication to cilostazol: see SmPC. 22. Prohibited medications to cilostazol: see SmPC. 23. Active cardiac disease, e.g. atrial fibrillation, myocardial infarction in past 6 months, active angina, symptomatic cardiac failure. 24. Bleeding tendency, e.g. known platelets200 mmHg ISMN exclusion criteria: 7. Definite indication for ISMN: i.e. already prescribed. 8. Definite contraindication to ISMN: see SmPC. 9. Prohibited medications to ISMN: see SmPC – phosphodiesterase-5-inhibitor, e.g. sildenafil, tadalafil and verdenafil.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility: Recruitment of 400 patients from 25 UK sites at 6 months, information collected from the trial database. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Retention: >90% participants at end of trial/6 months, information collected from database following the Day 183 follow-up. 2. Adherence: >75% of participants are taking >50% trial dose, information collected from database following week 1-2, week 3-4 and Day 183 follow-ups. 3. Completeness of primary clinical outcome: >85% of participants have a DSM-5-7L ordinal cognition scale at end-of-trial, information collected from database following the Day 183 follow-up. 4. Safety: All cause death; serious adverse events targeted drug-related adverse events (headache, loose stools, palpitations, nausea, dizziness, falls), information collected from database following week 1-2, week 3-4 and Day 183 follow-ups. 5. Proof-of-concept: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 7-level ordinal cognition scale at end-of-trial, information collected from database following week 1-2, week 3-4 and Day 183 follow-ups. | — |
Countries
England, Northern Ireland, Scotland, United Kingdom
Outcome results
None listed