New study underway to find best treatment for wake-up stroke patients

A new clinical study that could improve outcomes for people who have a stroke in their sleep is now underway, thanks to more than £320,000 funding from the British Heart Foundation (BHF).

Researchers at the University of Leicester have begun the three-year trial in the UK, which will study the best treatment for people who have an ischaemic stroke in their sleep and wake up with symptoms – also known as a wake-up stroke. 

An ischaemic stroke is the most common kind of stroke and occurs when an artery that supplies blood to the brain becomes blocked by a blood clot. 

People who have an ischaemic stroke when awake are usually given a clot-busting medicine called alteplase to restore blood flow to the brain and reduce the risk of death and long-term disability. Currently, alteplase must be given within 4.5 hours of symptom onset to have the best chance of being beneficial. 

However, around one in five ischaemic stroke patients are known to have had a wake-up stroke. Those who suffer a wake-up stroke are not currently routinely given clot-busting therapy, as it is not known when the stroke took place and whether clot-busting treatment would be effective. Instead, these patients receive standard care, which includes aspirin and admission to a stroke ward, along with rehabilitation and treatment to prevent recurrent stroke, if necessary. 

A recently completed study, which saw some wake-up stroke patients receive an MRI brain scan, has however shown benefit of clot-busting treatment in selected patients with wake-up stroke. 

The new clinical study tests a different clot-busting medicine, tenecteplase, in people who have had a wake-up stroke, and will use CT brain scans, routinely used in the assessment of acute stroke, to selected patients. Tenecteplase will be given by a single injection within 4.5 hours of the person waking with symptoms.

Patients will be randomly assigned in hospital to receive usual care, or usual care plus tenecteplase.  When they are discharged from hospital, each person’s recovery will be assessed. Then three months later, the patient or their relative will be contacted and asked about their recovery, their memory, how they feel and whether they require any additional help.

The study is part of a wider international clinical trial, called TWIST (Tenecteplase in Wake-up Ischaemic Stroke Trial), which is being co-ordinated by the University of Tromsø in Norway. The BHF’s funding will ensure the UK’s participation in this trial, which will involve 200 wake-up stroke patients admitted to at least 10 hospitals from across the country.

Ramji Khodiyar, aged 80, from Clarendon Park in Leicester, is the first patient in the UK to take part in the study. Ramji suffered a wake-up stroke on 14th September and was admitted to Leicester Royal Infirmary. The event has left Ramji finding it difficult to speak and swallow, and he also has problems with movement on the right side of his body.He was assigned to receive tenecteplase along with standard care, and his recovery is now being assessed by researchers.

Ramji’s son, Ashwin Khodiyar, aged 59, said: “On the morning of the stroke, my son, Jaymal, realised that dad hadn’t woken up at his usual time and went into his room to find that the right side of his face was swollen. When he woke, he was also struggling to speak.

“He received a CT scan at the hospital where they found a small clot in his brain and it was confirmed he had suffered an ischaemic stroke in his sleep. It was a shock to us, because my father is always up and about and keeps himself fit. He received a heart bypass around 20 years ago, but other than that, he’s not had any major health problems. He’s not one to stay still and he had been gardening the day before the stroke. 

“We were told about the study funded by the BHF and after some thought, we consented for dad to take part and receive tenecteplase. Dad is now receiving physiotherapy and his progress has been good so far. It’s great to hear that this trial could result in better treatment for people like my dad and we hope that his involvement will help others affected by this.”

The UK arm of the research is being led by Professor Thompson Robinson, Head of Department of Cardiovascular Sciences and Professor of Stroke Medicine at the University of Leicester.

Professor Robinson, who is also an honorary consultant physician at Leicester’s Hospitals, said: “Stroke is a leading cause of death and disability worldwide, with wake-up stroke affecting at least 20% of all patients. There are reasons to expect that wake-up stroke patients will benefit from clot-busting therapy, with a recent trial showing benefit in patients selected by MRI scans. The TWIST trial is using brain CT scans, the more commonly available type of brain scan, to assess patients. 

“If we find that tenecteplase is an effective treatment, this could have a major health benefit in reducing the likelihood of post-stroke death and disability for people who have suffered a wake-up stroke.”

Dr Shannon Amoils, Senior Research Advisor at the BHF, added: “Stroke causes over 38,000 deaths in the UK each year. The condition is a major cause of disability, with over a million UK stroke survivors. 

“This trial, where UK researchers are joining forces with stroke researchers from across Europe, could be vital in finding a new treatment and improving the outcomes for the thousands of people who have a stroke in their sleep.

“Funding for this research has only been made possible by the fantastic generosity of the public. We rely on their support to drive forward research programmes in our mission to beat heartbreak forever and ensure that we keep hearts beating and blood flowing.”

The BHF currently funds around £19 million of research into preventing and treating stroke.

This study is supported at Leicester’s Hospitals by the NIHR Leicester Clinical Research Facility.