Trial to test whether leg cream drug can halve repeat stroke risk

A US trial will test whether cilostazol, a drug used to treat symptoms of peripheral artery disease, can reduce the risk of a second ischaemic stroke.

UC San Francisco is preparing to enrol patients in the study, which will involve more than 2,000 participants across approximately 100 sites.

Previous studies in Japan, China and other East Asian countries have suggested that cilostazol could reduce stroke recurrence. Researchers now want to establish whether similar benefits can be achieved in a more diverse US population.

A second ischaemic stroke is associated with twice the risk of death and three times the risk of long-term disability compared with a first stroke.

The trial will include people diagnosed within the previous six months with an ischaemic stroke or high-risk transient ischaemic attack (TIA).

Both conditions involve a blood clot or narrowing of an artery that restricts oxygen-rich blood flow to the brain.

Ischaemic strokes account for approximately 87 per cent of all strokes in the US.

Cilostazol is already approved to treat leg cramping and numbness associated with peripheral artery disease.

Researchers hope it could also help prevent further strokes, potentially reducing recurrence by 50 per cent.

Anirudh Sreekrishnan, director of the UCSF Stroke Clinic and site principal investigator, explained why preventing another stroke is important for recovery.

He said: “After a first stroke, the brain relies on neuroplasticity to use surrounding tissue to rewire undamaged brain networks to take over lost functions, like movement and speech.

“With a second stroke, these newly recruited pathways may be further damaged, leading to fewer healthy nerve cells. The brain loses its ability to compensate, making recovery slower and more challenging.”

Neuroplasticity refers to the brain’s ability to reorganise its connections following injury, allowing undamaged networks to take over lost functions.

The new trial follows earlier research suggesting that adding cilostazol to standard stroke prevention medication could reduce recurrence.

A Japanese study published in 2019 compared patients receiving aspirin or clopidogrel, medications that help prevent blood clots, with those receiving standard treatment alongside cilostazol.

Over four years, 11.4 per cent of patients receiving standard treatment experienced another stroke, compared with 4.7 per cent of those also taking cilostazol.

Rates of side effects, including serious bleeding, were similar between the groups.

Cilostazol may offer additional protection by helping preserve the lining of arteries in the brain without increasing the risk of brain bleeds.

However, the Japanese study was not a double-blind, placebo-controlled trial, in which neither patients nor doctors know who is receiving the active treatment.

Anthony Kim, medical director of the UCSF Comprehensive Stroke Center, said this was an important limitation.

He said: “Without this gold standard, there’s the potential to introduce bias.”

The earlier study also involved a less diverse population than the forthcoming US trial.

Sreekrishnan noted that two-thirds of participants were male and all were Japanese.

He said: “It is not yet known if this level of effectiveness can be replicated in the United States with its racially diverse population.”

The new study will use a double-blind, placebo-controlled design to assess whether the earlier findings can be reproduced in the US.

Participants will be followed for up to five years.

The trial is being conducted through NIH StrokeNet, a national research network focused on stroke prevention, acute treatment and recovery, with funding from the National Institute of Neurological Disorders and Stroke.

Kim is the principal investigator for StrokeNet’s regional coordinating centre and oversees trial execution at UCSF and its partner sites.

The national trial is led by Adam de Havenon and Kevin Sheth of Yale University, alongside Maarten Lansberg of Stanford University.

The study will help determine whether adding cilostazol to standard treatment can reduce recurrent strokes and the associated risks of neurological damage and long-term disability.