LACunar Intervention (LACI-2) Trial-2: Assessment of safety and efficacy of cilostazol and isosorbide mononitrate to prevent recurrent lacunar stroke and progression of cerebral small vessel disease.
University of Edinburgh
Duration of Study in the UK
3 years, 0 months, 1 days
Summary of Research
Why: About 35,000 people each year in the UK have a type of stroke, called ‘lacunar’ or ‘small vessel’ stroke, which is different to other common types of stroke and for which there is no proven treatment. Small vessel stroke is caused by damage to the lining of the tiny blood vessels in the brain that stops the vessels functioning normally and damages the brain. This could be the cause of up to 45% of all dementias.
What: Two drugs that are commonly used in other vessel diseases may help improve small vessel function and prevent worsening of brain damage. Patients that join the study will be allocated open label to one of a possible four options:
• cilostazol only
• isosorbide mononitrate only
• both cilostazol and isosorbide mononitrate
• neither drug
Patients will stay in the study taking their allocated medicine for 1 year.
Who: In the current phase, up to 400 patients aged over 30 years, diagnosed as having had a lacunar stroke. Patients joining the study must be able to give consent themselves and be independent in activities of daily living at the time of recruitment.
Where: The trial will be conducted at hospitals with stroke specialists in the UK.
How: Eligible consented patients will be randomised by web-based system, prescribed trial drug, followed up locally, then centrally for one year to find out if we can recruit, retain and follow-up patients in sufficient numbers, if patients tolerate the trial drug(s), and to obtain safety, efficacy and outcome data prior to a large definitive trial. The trial has been designed by experienced stroke trialists and piloted.
Summary of Results
Annually in the UK, about 35,000 people have a ‘lacunar’ or ‘small vessel’ stroke, which is different to other types of stroke, possibly causes dementia, and has no specific treatment. It is probably caused by damage to the lining of the tiny brain blood vessels inside the brain, called small vessel disease, stopping them supplying oxygen and nutrients properly to the brain.
We designed the LACI-2 trial to test two promising medicines used for other conditions (isosorbide mononitrate (ISMN) and cilostazol) to gather information on practicality and safety, and plan a large trial to see if these drugs can improve outcomes after lacunar stroke. Importantly, if the drugs help patients with lacunar stroke, then they might also help patients with other forms of small vessel disease.
LACI-2's main aim was to see if enough participants could join the trial, could take the medicines for one year, if the medicines were safe, and if the medicines might help prevent patients from having another stroke, loosing their thinking skills or memory and their independence.
LACI-2 recruited 363/400 planned participants, 98% stayed in the trial, 95% could take the drugs for a year, and there were no safety concerns.
At one year, participants given ISMN had fewer strokes and better thinking skills, those given cilostazol were more independent, and those given both drugs had better thinking skills and were more independent, as well as several other benefits.
We will now do a large clinical trial, LACI-3, to confirm these findings in patients with lacunar stroke; we will also start similar trials with these drugs in patients with other types of small vessel disease to see if they benefit small vessel disease found on scanning and that can cause loss of thinking skills and dementia.
East Midlands - Nottingham 2 Research Ethics Committee
Date of REC Opinion
2 May 2017
Further Information Favourable Opinion