Open studies

Tranexamic acid for Hyperacute Spontaneous Intracerebral Haemorrhage (TICH-3).

ICH is a medical emergency and causes more than 1.7 million strokes worldwide per year3, 4 with a mortality of over 40%.5 More than 10,000 people suffered an ICH last year in England. There is no effective drug treatment for ICH, and only a small proportion of patients benefit from surgery. Haematoma growth is common, occurs early,6, 7 and is the commonest cause of death after ICH. It can potentially be prevented by haemostatic therapies, which are effective in other bleeding conditions.8, 9

Time from symptom onset, baseline haematoma growth and anti-thrombotic therapy use are all independent predictors of haematoma growth.10 The Computed Tomography (CT) spot sign can also improve the prediction model but has not been successful in previous trials11 and is not routinely performed in clinical practice.

ICH related disability causes massive burdens to the affected individual, their family and society. ICH was identified as a priority research area by The Stroke Association, with interventions to stop bleeding as a treatment target.12 The incidence of ICH is increasing due to high blood pressure and the ageing population, with ICH-related death and disability set to rise.13, 14 Recent improvements in stroke pathways have led to rapid imaging, with early diagnosis providing an opportunity to rapidly administer treatments. Implementation of an effective haemostatic therapy such as tranexamic acid (TXA) is therefore possible in ICH.

The proposed study will build on experience from the NIHR HTA funded TICH-2 trial,15 streamline trial methods and enable rapid enrolment of those most likely to benefit. If the haemostatic effect demonstrated in TICH-2 (with reduction in early death) is confirmed in TICH-3, this could change clinical practice globally. By enrolling participants earlier and excluding those with established large HVs, TICH-3 targets patients with the greatest potential to benefit.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

Can we improve the prediction of adverse outcomes for people following a stroke to optimise their treatment and care?

How is it of relevance and importance to patients and public?

Following a stroke, people are at a higher risk of developing certain conditions including heart failure, another stroke and atrial fibrillation, a type of irregular heart rhythm. In the proposed study, we will look at factors which may increase a person’s risk of such conditions following stroke. From this, we will determine if we can improve risk scores for these conditions for people post-stroke. This could help doctors decide what treatments are best.

Who would be eligible?

All adults at participating hospitals who have had an ischaemic stroke (where the stroke is caused by loss of blood flow to the brain) or a transient ischaemic attack (‘mini-stroke’) confirmed by a stroke doctor. All patients will be asked to take part in the study, or their family members may be asked to provide advice on their behalf if the patient is unable to.

Where is the study being conducted?

At participating hospitals.

What will the participants undergo?

At the time of stroke, patients have a lot of information collected about their health, we will copy information from patient’s medical records about their health after they agree to take part in the study. We will also ask the patients or their family members to complete some additional brief questionnaires about their quality of life, wellbeing and fatigue. Some questionnaires such as for cognitive function are already collected for patients following a stroke, but where this information has not been collected, we will collect it for the study. We will ask the patients if we can contact them in 12-months to repeat the questionnaires and information collected about their health.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

PREPARE: imPRoving End of life care Practice in stroke cARE

21% of stroke patients die within 30 days of having their stroke. Stroke can make end-of-life care complex. Death after stroke may happen:
• Suddenly and quickly
• After gradually worsening health, or
• After ups and downs in a person’s condition

Staff may be unsure when to move from active treatment to end-of-life support. Complications after stroke, affecting speech, language and awareness, may make it difficult for patients and family to discuss end-of-life care. Additionally, staff may lack the skills and confidence for these discussions.

There is little evidence to guide how stroke end-of-life care is provided. We will explore what challenges stroke creates, and how recent changes to general end-of-life care work with stroke patients. The project will investigate what patients, carers and staff think helps and hinders, and what they think people need and would prefer.

We will:
1. Review research on the signs someone is likely to die within 30 days following hospital admission with stroke.
2. Review research about the needs of stroke patients and their families towards the end-of-life, and staff experiences of delivering care.
3. Survey UK hospital stroke units on current end-of-life care.
4. Explore healthcare professionals’ views and experiences of giving stroke end-of-life care, including decision-making and goal-setting.
5. Talk with patients, families and clinical experts about the research findings to identify the things needed to develop a package of stroke end-of-life care and support and decide how best to measure the patient/carer experience of the care package.

We aim to design and test the stroke end-of-life care and support package in a later, larger study. Our study Patient and Public Involvement (PPI) group, including bereaved relatives and survivors of serious stroke, will continue to support us, to ensure the research is relevant, moral, successful and makes a difference.

Clot busting (Thrombolytic) drug treatment given in the first few hours after onset of stroke caused by a blockage in a blood vessel in the brain greatly improves the chances of recovering to independence. Treatment is effective for patients of all ages and severities of stroke. The quicker treatment can be given, the greater the benefit. Stroke units in the UK now treat up to 20% of stroke patients with thrombolytic drugs.

However, it may be possible to improve upon the drug that is currently used (alteplase, also known as rtPA). Newer clot busting drugs have been developed, and have replaced alteplase in other fields of medicine. We, and others, have investigated one of these drugs, called tenecteplase, in small studies in stroke patients, and it appears possible that tenecteplase is potentially more effective and also safer than alteplase, causing less disruption of the body’s blood clotting system, and possibly fewer brain haemorrhages. We now wish to test tenecteplase in a large clinical trial to establish whether it is better than alteplase. This will involve a large number of hospitals in the UK, and possibly overseas. People who are considered suitable for clot busting treatment will be allocated at random to receive either the current standard treatment with alteplase, or tenecteplase, and will be followed up for the first 90 days to measure the effects on recovery.

Even if there are no significant differences between tenecteplase and alteplase, tenecteplase is less expensive and much easier to give (needing a single injection only, whereas alteplase has to be given as an injection followed by a longer injection over an hour). This alone would have worthwhile benefits.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

CONVINCE – A randomised clinical trial of low dose colchicine for secondary prevention after stroke.   Patients who have recently had a stroke or transient ischemic attack may be invited to take part in the CONVINCE Study. To reduce the risk of another stroke, the standard care often includes medicine that slows clotting (e.g aspirin), reduces cholesterol (e.g statins), and lowers blood pressure. The purpose of this study is to compare an anti-inflammatory medication called colchicine used with standard treatment to standard treatment is no placebo medication.  This is a research study because colchicine has not yet been proven to prevent stroke/heart attack after stroke. It is expected that about 2623 patients from at least 5 countries will participate.  The study medicine is colchicine. It works by blocking the action of proteins (tubilins) that play important roles in inflammation. Inflammation increases the risk of stroke and heart attack.  At low doses similar to the dose in this study, colchicine has been safely used for many years in the treatment of joint diseases, such as gout and Familial Mediterranean Fever. It is taken by mouth, once a day with a glass of water. The dose in the study is 0.5 mg (one tablet per day).  Participants will be followed for 12-60 months.  Participants will be asked to attend clinic visits at 1 month and every 6 months until the end of the study. At each visit study staff will:

If assigned to colchicine, check that the participant is taking it and other medicines.

Collect information about any new medical problems , or possible side effects from medicines.

Provide the participant with a new supply of colchicine, if they are assigned to it.

Check heart rate, blood pressure and level of independence.

A blood test will be taken at the first visit and once per year thereafter.

This research is funded by the Health Research Board of Ireland.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

Disease of the small blood vessels in the brain (SVD) is an important cause of stroke, cognitive impairment and dementia. Therefore SVD is a major public health problem. Researchers do not yet fully understand what causes SVD and this is an important reason why there are no specific therapies to delay its progression. Genetic studies provide the opportunity to identify entirely novel disease mechanisms and thereby may allow us to develop new treatment approaches. In addition, the identification of novel genes might allow us to identify individuals at high risk in whom we could institute specific treatments or particularly intensive risk factor prevention.

However, previous large-scale genetic studies have been largely unsuccessful in SVD, which is probably due to inadequate phenotyping of SVD, disease heterogeneity and relatively small sample sizes.

This study is part of a larger project, recently funded by a British Heart Foundation programme grant awarded to Professor Hugh Markus. We are going to study the genetic basis of SVD defined using detailed phenotyping. We are going to perform a Genome Wide Association Study, which can identify up to one million variants across somebody’s genomes. In addition we are going to apply powerful new computer methods that make efficient use of disease heterogeneity. In this study we aim to increase the sample size by recruiting another 1000 MRI-defined SVD stroke cases and thereby to increase the ability to detect novel genes. Details about the stroke, cardiovascular risk factors, family history and other health details will be collected and 10 ml of blood will be taken from a vein.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

Predicting language outcome and recovery after stroke.  As part of the study patients have an MRI and language tests in London to understand how the brain recovers speech and language after a stroke so that in future, stroke patients can be told how long their recovery will take.

Full title: EdoxabaN foR IntraCranial Haemorrhage survivors with atrial fibrillation (ENRICH-AF)

Summary: This study will assess if the use of Edoxaban (an anticoagulant drug that slows blood clotting) reduces the risk of
stroke in people with both a previous intracranial bleed and atrial fibrillation (AF), compared to treatment without anticoagulant drugs. People with AF have a high risk (1 in 15/year) of stroke because blood clots that form in the heart can travel to the brain and block a blood vessel there. Anticoagulant drugs are widely used to prevent clots from
forming and to reduce the chance of blocking blood vessels in people with AF. However, they carry a small risk of bleeding. For most people with AF, the large benefit from preventing stroke cause by blood vessel blockage is much more than the harm caused by bleeding into the head. Using anticoagulant drugs in people who have had bleeding in the head needs to be researched to know if it is beneficial overall or not. In patients with AF and previous bleeding into the head, some doctors currently recommend aspirin or similar drugs that belong to a group called antiplatelet drugs.

These drugs are less effective in preventing clots in AF compared to anticoagulant drugs. Other doctors may recommend no drugs to slow blood clotting (meaning neither anticoagulation nor aspirin or similar drugs).  Edoxaban, a new direct oral anticoagulant, is a promising treatment option in this population as it is highly effective for blood clot
prevention and is associated with low rates for bleeding in the head (4 out of 1,000 patients/year). Edoxaban is approved by the MHRA and recommended for the prevention of stroke in patients with AF. However, Edoxaban has never been previously tested in people who have suffered bleeding in the head. ENRICH-AF will discover if Edoxaban is beneficial overall for these patients.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

Full title: OPtimal TIMing of Anticoagulation after acute ischaemic Stroke: a randomised controlled trial (OPTIMAS Trial)

Summary: Atrial fibrillation (AF) is a type of irregular heartbeat that can cause blood clots to form in the heart. The movement of these clots can block blood vessels in the brain, causing a type of stroke known as a cardioembolic ischaemic stroke. Direct oral anticoagulants (DOACs) are medicines prescribed to prevent further strokes in people with AF who have had a stroke, and are usually started 7-14 days after stroke as standard care. However, it is unclear if starting DOAC treatment earlier than standard care could benefit patients; early treatment (up to 4 days after stroke) may lower the risk of further stroke, but may increase the risk of major bleeding, especially in the brain.

This trial aims to compare the effectiveness of early DOAC treatment to prevent recurrent stroke and systemic embolism (i.e. a blood clot in an artery) in patients with acute ischaemic stroke and AF with that of standard timing of DOAC treatment. The four DOACs that are usually prescribed to prevent recurrent stroke are dabigatran, apixaban, rivaroxaban, edoxaban, and they will be used according to their drug licenses in this trial. The choice of DOAC will be decided by the treating doctor, but the timing of treatment will be allocated to either early or standard. It is expected that 3500 adult patients (> = 18 years) admitted to +100 participating acute stroke units with acute ischaemic stroke and AF will be screened for eligibility, and consented (by patient or legal representative if the patient is too unwell to make their own decisions). They will then be entered into the trial receive early or standard DOAC treatment. Patients who cannot have anticoagulant treatment because of specific conditions such as an increased tendency to bleed or poor liver function will be excluded.

Participants will be followed up at 90 days post-study entry to collect information on how well they have taken DOAC treatment (known as adherence), side effects, and whether they have had specific clinical events such as stroke, bleeding, and systemic embolism. This information will allow the researchers to calculate the rate of newly-occurring stroke, bleeding in the brain (symptomatic intracranial haemorrhage), and systemic embolism in the 90 day treatment period for each of the two groups (early and standard) so they can be compared. The impact of early versus standard treatment on participants’ quality of life and cognition will also be investigated by using specific assessments.

For more information please contact the Clinical Research Nurse on clinical.research@ydh.nhs.uk.

Studies in follow up