Lacunar (small vessel) ischaemic stroke Nervous System Diseases
Conditions
Interventions
The intervention involves random allocation to one of the four treatment groups, in addition to the guideline standard care after lacunar ischaemic stroke, using an electronic randomisation system:
1.
Sponsors
University of Edinburgh
NHS Lothian
Eligibility
Sex/Gender
All
Age
30 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. Age =30 years 2. Clinical stroke syndrome compatible with a lacunar stroke and brain imaging (MRI preferred but CT allowed) at the time of the stroke shows a relevant recent small subcortical infarct, or if no relevant infarct then no other explanation for symptoms is seen 3. Genetic forms of SVD (e.g. CADASIL) may be included if they present with a lacunar stroke 4. Capacity to give consent in the opinion of the PI or any delegated member of the research team
Exclusion criteria
Exclusion criteria: General Exclusion Criteria: 1. Less than 24 hours since onset of the lacunar stroke or patient on dual antiplatelet drugs 2. Stroke mechanism with definite treatment indication (e.g. cardioembolism, ipsilateral carotid stenosis) 3. Other explanation for the lacunar stroke symptoms (i.e., recent cortical infarct, haemorrhage or tumour) 4. Other active neurological disease (e.g., brain tumour, multiple sclerosis, recurrent seizures, neurodevelopmental disorder - well-controlled epilepsy present prior to the lacunar stroke, a single seizure at onset of the stroke, or provoked seizure, is not an exclusion) 5. Contraindication to both trial drugs in section 4.3 of the SPCs (patients with a contraindication to one trial drug may still be randomised to the other trial drug) 6. Indication for either trial drug (patient already prescribed one trial drug may still be randomised to the other trial drug) 7. Dependent (mRS>2) 8. Clinical diagnosis of dementia 9. Planned surgery during the trial period including carotid endarterectomy. Note 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 10. Unable to swallow 11. Diagnosis of hypotension, defined as sitting systolic blood pressure less than 100mmHg 12. History of drug overdose or attempted suicide 13. Unlikely to be available for follow-up at 18 months 14. 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 15. Pregnant, breast-feeding, or of child-bearing potential and not using highly effective contraception 16. Renal impairment (creatinine clearance <25 ml/min) 17. Hepatic impairment 18. Currently prescribed dual antiplatelet treatment (single antiplatelet is not an exclusion); patients can be randomised into the trial once the 28-day period of dual antiplatelet for guideline secondary prevention following the acute lacunar ischaemic stroke has completed 19. Previously enrolled in LACI-3 20. Enrolled in a study that precludes co-enrolment with LACI-3 Cilostazol Exclusion Criteria (still allows randomisation to ISMN): 1. Definite indication for (i.e., already prescribed) Cilostazol, or definite contraindication to Cilostazol as per SPCs section 6.1.8. 2. Prohibited medications to Cilostazol (see sections 4.5 of the appended SPCs and protocol section 6.7.3) 3. Active cardiac disease (atrial fibrillation, myocardial infarction in past 6 months, active angina, symptomatic cardiac failure) 4. Bleeding tendency (e.g., known platelets <100, active peptic ulcer, history of intracranial haemorrhage such as subdural haematoma, subarachnoid haemorrhage, intracerebral haemorrhage, but not asymptomatic haemorrhagic transformation of infarction or a few microbleeds, taking anticoagulant medication) ISMN Exclusion Criteria (still allows randomisation to Cilostazol): 1. Definite indication for (i.e., already prescribed) ISMN, or definite contraindication to ISMN as per SPCs 2. Prohibited medications to ISMN (see sections 4.5 of the appended SPCs and protocol section 6.7.3)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cognitive impairment after lacunar ischaemic stroke will be evaluated at 18 months after randomisation using the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) scale operationalised, a 7-level ordinal cognitive impairment scale using subscores of the Telephone Montreal Cognitive Assessment (tMOCA), Telephone Interview for Cognitive Status (TICS), animal naming, clinical dementia diagnosis measured at 6, 12 and 18 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measures: The secondary outcomes will be evaluated at 18 months after randomisation: 1. Dependency (defined as mRS>2) is measured using a Modified Rankin Score at 6, 12 and 18 months 2. Cognitive impairment or dementia are measured at 6, 12 and 18 months using: 2.1. Telephone-Montreal Cognitive Assessment (t-MOCA) 2.2. Telephone Interview for Cognitive Status (TICS) 2.3. Concentration (from Mini-Mental State Examination [MMSE]) 2.4. Animal naming 3. Clinical outcomes are measured using postal/telephone questionnaires and medical notes during 18 months after randomisation: 3.1. Recurrent ischaemic stroke or transient ischaemic Attack (TIA) or haemorrhagic stroke 3.2. Fatal or non-fatal myocardial infarction (MI) 3.3. Death, due to vascular and any cause 4. Safety outcomes are measured using reported Serious Adverse Events (SAEs) during 18 months after randomisation 5. IMP symptoms are measured using telephone/postal questionnaires at 1-2 weeks, 3-4 weeks, and 6, 12 and 18 months 6. Quality of life is measured using: 6.1. Stroke Impact Scale (individual domains and global) postal questionnaire at 6, 12 and 18 months 6.2. EQ5D-5L, EQ-VAS of the EuroQol paper questionnaire at randomisation and 18 months 6.3. Mood is measured using the ZUNG depression rating scale at 6, 12 and 18 months 6.4. Composite of recurrent stroke or TIA, MI, death, dependency (mRS>2), cognitive impairment at 18 months after randomisation 6.5. Global Clinical Outcome of recurrent stroke or TIA, MI, death, mRS>2, cognitive impairment, QoL, mood (ZUNG) at 18 months after randomisation 6.6. Health economic usage using a postal questionnaire is measured 18 months after randomisation Tertiary outcome measures: Blood pressure measures will be evaluated at 18 months after randomisation using blood pressure measurements made by participants or available from GP or hospital medical records as a part of the routine stroke prevention therapy at randomisation, 1-2 weeks, 3-4 weeks and at 6, | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactKasia Adamczuk
Outcome results
None listed