LACI-2

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. We think that small vessel stroke is caused by damage to the lining of the tiny blood vessels deep inside the brain that stops them functioning normally. Some drugs that are commonly used in other blood vessel diseases may help improve small vessel function and prevent worsening of brain damage. One drug (cilostazol) has been tested in patients with stroke in the Asia Pacific countries but not on dementia; the other drug (isosorbide mononitrate) is widely used in the UK for heart disease but not stroke. We have set up a clinical trial to test if the study methods are practical so that patients and trial centres can follow the procedures, and to confirm how many patients have more stroke-like symptoms or experience worsening of their thinking skills. This information is needed to be sure that a very large clinical trial to find out if these drugs can prevent worsening of small vessel disease will be possible.

 

Chief Investigator: Professor Joanna M Wardlaw

 

Number and location of participating sites (by region/ country): 26 UK sites

EudraCT number: 2016-002277-35

 

ISRCTN number: 14911850  http://www.isrctn.com/ISRCTN14911850?q=&filters=conditionCategory:Nervous%20System%20Diseases&sort=&offset=2&totalResults=635&page=1&pageSize=10&searchType=basic-search

 

Funder: British Heart Foundation

Start and End date

Of grant award: March 2018 - August 2022

Of recruitment: January 2018 - May 2021

 

Current Status: Published

To see the results of the trial please see the publication:  https://pubmed.ncbi.nlm.nih.gov/37222252/

“Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial”  

 

LACI 2 Trial Lay Summary

Why did we want to do the trial?

Every year in the UK, many people (about 35,000) have a type of stroke called ‘lacunar’ or ‘small vessel’ stroke.  This is different to other common types of stroke and there is no specific treatment.   Small vessel stroke is probably caused by damage to the lining of the tiny blood vessels deep inside the brain that stops them working properly. This not only causes stroke but, perhaps more importantly, may also cause problems with thinking and walking and possibly causes dementia.   We  wanted to see in LACI 2 whether we could design a trial to test two promising medicines that are already commonly used for other conditions- (isosorbide mononitrate (ISMN) and cilostazol). This was the second part of three studies we plan to do, to see if these drugs improve outcomes after stroke. 

 

How did we do it?

We were awarded funding from the British Heart Foundation and we built up a network of experts from across the UK to run the trial.  Twenty-six hospitals invited patients who had had a lacunar/small vessel stroke to take part in the trial. 

Participants were put at random (like flipping of a coin) into one of four groups to take ISMN or cilostazol or both medicines or no medicine at all. The doctors and participants both knew which medicine the participant was taking but the researchers reviewing their symptoms and thinking skills didn’t know so they could fairly review any changes. 

The main purpose of the trial was to see whether it was possible to invite 400 participants into the trial and whether they managed to stay on the medicines for one year.   We also wanted to see how well the medicines seemed to work by looking at whether there was an overall difference between the groups in how many people:

1. Developed a new stroke related health problem (Died, had another stroke or heart attack, developed thinking problems or dementia, or needed help with daily activities)
2. Saw changes in their quality of life. 

What did we find?

Between 05 February 2018 and 31 May 2022, LACI-2 recruited 363 out of the 400 participants we hoped to invite into the trial (this number was probably affected by the covid pandemic).  Most participants (98%) stayed in the trial for one year and 95% of participants managed to take at least half the medication they were given.  Doctors reviewed any side effects of the medicines and they saw nothing that made them worry that the tablets were not safe to use for patients with this type of stroke.

The trial statistics expert then compared each group to see if there was any difference in stroke related health problems:

 

ISMN tablets versus no tablets

• Participants given ISMN tablets were less likely to have another stroke, had better thinking skills and reported a better quality of life than those given no ISMN tablets. 

Cilostazol tablets versus no tablets

• Participants given cilostazol tablets were less likely to need support to do everyday things than those given no cilostazol tablets.

 

Both Cilostazol and ISMN together versus no tablets

• Participants given both ISMN and cilostazol tablets together had fewer stroke related health problems than the group with no tablets.  This was the only group where we saw an overall difference. 
• Participants in this group where less likely to need support to do everyday things or have thinking problems.  They also reported having a better quality of life than the group taking no tablets.

 

What does this mean?

Our findings suggest that it is possible to complete trial of these medicines in patients with lacunar/small vessel disease stroke and that most patients are able to take the tablets with no serious side effects.  It suggests that taking both medicines at the same time might make the biggest difference to stroke related health problems and might be useful to help prevent dementia brought on by this type of stroke but we cannot be certain of this.   We would now want to do a similar trial with a much larger number of participants to try to prove that these medicines work in the way we think they do.

 

UK GDPR Privacy Statement: If you have participated in this study and would like to read how it complies with UK GDPR, please read this document.

 

Sponsor: University of Edinburgh/NHS Lothian (ACCORD)    http://www.accord.ed.ac.uk/

Chief Investigator: Professor Joanna M Wardlaw, Neuroimaging Sciences, University of Edinburgh, Centre for Clinical Brain Sciences (CCBS), Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB; Tel: +44 (0)131 465 9599; Email: Joanna.Wardlaw@ed.ac.uk

Trial Manager: Kat Oatey, Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Level 2, Nine Edinburgh BioQuarter, 9 Little France Road, Edinburgh EH16 4UX; Tel: 0131 651 9913; laci-2@ed.ac.uk

 

ECTU Involvement: Trial Management and Follow-Up

(UKCRC)