Awarded Clinical Study Grants

Grants awarded by the Clinical Studies Committee are listed below.

November 2018

The TIGHT-K STUDY. Arrhythmias on the cardiac intensive care unit - does maintenance of high- normal serum potassium levels matter?

Dr Benjamin O'Brien, Queen Mary, University of London

£1,200,000 over 4 years, 6 months

CS/18/3/34063

Atrial fibrillation (AF) occurs in at least one in three patients after cardiac surgery, and is associated with increased mortality, prolonged intensive care unit and hospital stay, and increased cost of care. To try and reduce AF incidence in these patients, serum potassium levels are commonly maintained at the high-end of normal (4.5 – 5.5 mEq/L). However, such potassium supplementation is without proven benefit, is unpleasant for patients to take, and can have negative consequences. This randomised, multicentre, non-inferiority trial will investigate, in around 1700 patients, whether maintaining serum potassium ≥3.6mEq/L (the lower end of normal) is no worse than maintaining potassium levels at 4.5-5.5mEq/L in terms of the incidence of new onset atrial fibrillation in the first 120 hours after coronary artery bypass surgery

Computed tomography coronary angiography for the prevention of myocardial infarction, The SCOT-HEART 2 Trial

Professor David Newby, University of Edinburgh

£ 943,260 over 8 years

CS/18/4/34074

Prevention of cardiovascular disease is currently guided by probabilistic risk scores that over and under treat individuals, commit most middle-aged people to drug treatment, and have little evidence base. This team has shown that the use of computed tomography coronary angiography (CTCA) is associated with changes in the diagnosis and treatment of patients presenting with stable chest pain, leading to a marked reduction in the future risk of myocardial infarction. This randomised controlled trial will compare two strategies of targeting preventive therapies: a cardiovascular risk score versus screening with CTCA in 6000 middle-aged individuals at risk of cardiovascular disease. The trial will determine if CTCA guided management is associated with better targeted intervention and fewer future coronary heart disease events than the current standard of care using a cardiovascular risk score.

Multicentre, prospective randomised open label, blinded-endpoint (PROBE) controlled trial of thrombolysis with low dose Tenecteplase (TNK-tPA) versus standard of care in the prevention of disability at 3 months in minor ischaemic stroke with proven acute symptomatic occlusion (TEMPO-2)

Professor Keith Muir, University of Glasgow

£ 488,647 over 4 years

CS/18/5/34081

Despite observations that patients with apparently minor or transient symptoms of acute ischaemic stroke are at significant risk of permanent disability, they are often not given thrombolytic drug treatment because there is currently limited evidence for its use in this context. Patients who have evidence of an intracranial vessel occlusion on CT angiography are at greatest risk of poor outcome. The TEMPO-2 trial will establish whether the thrombolytic drug tenecteplase results in a greater proportion of patients recovering to baseline function defined by day 90 modified Rankin Scale compared with standard medical care (expected to be antiplatelet therapy) among patients with minor stroke or transient ischaemic attack and an intracranial vessel occlusion on imaging. TEMPO-2 is an international, multicentre, prospective, randomised, open-label, blinded endpoint evaluation (PROBE) trial that will enrol 1274 patients across 50 sites in 6 countries.

Alteplase-Tenecteplase trial evaluation for stroke thrombolysis (ATTEST-2) imaging substudy

Professor Keith Muir, University of Glasgow

£551,803 over 2 years, 6 months

CS/18/6/34079

In acute ischaemic stroke, the current standard of care for intravenous thrombolysis is alteplase. While this significantly improves the likelihood of recovery without disability, it is less effective among people with larger blood vessel occlusions, administration is cumbersome, and the short half-life of the drug makes very rapid recanalisation less likely. Tenecteplase is a newer thrombolytic agent with superior pharmacological properties that is being compared with alteplase in the BHF-funded ATTEST-2 trial. This imaging substudy will support CT angiography, CT perfusion and MRI imaging of participants in ATTEST-2 at centres with research imaging capabilities. The substudy will investigate whether there are differences between tenecteplase and alteplase in early recanalisation, infarct volume and penumbral salvage.

The Early surgery in severe ASYmptomatic Aortic Stenosis trial- EASY-AS

Professor Gerry McCann, University of Leicester

£2,722,054 over 10 years

CS/18/7/33714

Aortic Stenosis is the commonest valve disease requiring surgery but the risks and benefits of a strategy of early Aortic Valve Replacement (AVR) versus watchful waiting in asymptomatic patients are unclear. The Early valve replacement in severe ASYmptomatic AS (EASY-AS) trial is a pragmatic, multicentre parallel group randomised controlled trial, which plans to recruit 2844 patients with severe asymptomatic aortic stenosis from secondary and tertiary hospitals in the UK. Participants will be randomised to receive either early AVR or a guideline recommended strategy of watchful waiting. They will be followed over a median of 5 years to measure the primary outcome, a composite of cardiovascular death and heart failure hospitalisation. A key secondary outcome will be disability-free survival. Initial funding supports a vanguard phase, which will assess the feasibility of recruiting 200 patients from 20 centres over the first 22 months of the trial. The results of this large pragmatic trial will address a key knowledge gap and inform national and international guidelines.

May 2018

Troponin in Acute chest pain to Risk stratify and Guide EffecTive use of Computed Tomography Coronary Angiography (TARGET-CTCA)

Professor Nicholas Mills, University of Edinburgh

£1,115,723 over 5 years 

CS/18/1/33711

Most patients presenting to hospital in the UK with symptoms suggestive of acute coronary syndrome will be discharged home without further investigation or treatment once myocardial infarction has been ruled out. A significant proportion of these patients will have unrecognised coronary artery disease (CAD), but the appropriate subsequent management of these patients is unclear and varies widely. High-sensitivity cardiac troponin concentrations below the threshold used to diagnose myocardial infarction are increasingly recognised as a powerful predictor of the future risk of major adverse cardiovascular events. It is proposed that, once myocardial infarction has been excluded, patients with acute chest pain and high-sensitivity cardiac troponin concentrations ≥5 ng/L may benefit from computed tomography coronary angiography to diagnose underlying CAD and direct subsequent management. This multi-centre randomised controlled trial will evaluate if this approach improves clinical outcomes in patients presenting to the emergency department with acute chest pain.

Start or STop Anticoagulants Randomised Trial (SoSTART) for atrial fibrillation after intracranial haemorrhage: safety phase

Professor Rustam Al-Shahi Salman, University of Edinburgh

£721,223 over 3 years

CS/18/2/33719

Atrial fibrillation (AF) confers a high risk of systemic embolism (mostly to the brain), especially in older people with other vascular risk factors. Oral anticoagulant drugs effectively prevent systemic embolism in people with AF. However, randomised controlled trials of oral anticoagulation for AF excluded people with intracranial haemorrhage (ICH), leaving uncertainty about the risks and benefits in this group. The SoSTART study will investigate whether starting oral anticoagulants after ICH in people with AF results in a beneficial net reduction of all serious vascular events compared with not starting anticoagulants. This safety phase of the SoSTART study will randomise ~190 participants with AF after ICH and measure the occurrence of all serious vascular events over at least 1 year to test whether starting oral anticoagulation is non inferior to avoiding oral anticoagulation for the primary outcome of recurrent ICH. If starting oral anticoagulation is sufficiently safe, the trial will proceed to a main phase to investigate net benefit.

November 2017

OPTIMAS: OPtimal TIMing of Anticoagulation after AF-associated acute ischaemic Stroke: a randomised controlled trial

Professor David Werring, University College London

£2,045,998 over 5 years

CS/17/6/33361

Oral anticoagulation is highly effective for long term stroke prevention in people with atrial fibrillation (AF) but the best time to start (or restart) anticoagulants after an acute ischaemic stroke is not known. Early anticoagulation (in the first few days) could prevent stroke recurrence but might increase the risk of symptomatic intracranial haemorrhage, including haemorrhagic transformation of the infarct. OPTIMAS will randomise 3474 patients with AF-related acute ischaemic stroke to early (≤4 days after a stroke) or later anticoagulation (5-14 days after a stroke) using direct oral anticoagulants (DOACs) to find out the optimal timing of anticoagulation after acute AF-related ischaemic stroke. The primary outcome will be a 90-day composite of recurrent ischaemic stroke, intracranial haemorrhage, systemic embolism, and death.

May 2017

How do arrhythmias and conduction disturbances contribute to death or rehospitalisation in patients discharged following an admission with acute heart failure? A prospective, observational, multi-centre cohort-study

Dr Roy Gardner, University of Glasgow

£429,737 over 4 years, 6 months

CS/17/4/33009

Arrhythmias are likely to have a major role in death and readmission to hospital in patients with heart failure (HF), but this issue has not been systematically studied. This prospective, observational, multi-centre cohort study will examine the role of arrhythmias in HF by undertaking continuous, long-term surveillance for arrhythmias using injectable cardiac monitors (ICMs). Patients will receive an ICM during an index admission for HF, and will be followed up for ≥2 years. The main analysis will be the association of arrhythmias with rehospitalisation and death. In patients who die, ICMs also record the terminal electrical rhythm. The identification of sudden deaths involving ICM-documented arrhythmic mechanisms will form a novel endpoint. This study may identify new targets for intervention in HF, and inform the design of randomised trials of pharmacological and device-based therapies.

Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Professor Thompson Robinson, University of Leicester

£323,014 over 3 years

CS/17/5/32826

Although thrombolytic therapy with alteplase given within 4.5 hours of ischaemic stroke onset improves clinical outcome, patients who have new symptoms on waking (wake-up stroke) are excluded; about 1 in 5 strokes present in this way. Tenecteplase is a new thrombolytic with potential advantages over alteplase: greater fibrin specificity, rapid action, longer half-life and single bolus administration. TWIST is an international, multi-centre, randomised, open-label, blinded endpoint trial of tenecteplase for acute ischaemic wake-up stroke. The trial is taking place in Norway, the UK and other countries in Europe. In total, 500 patients eligible for treatment within 4.5 hours of waking with symptoms will be randomly allocated to 0.25mg/kg bolus dose of tenecteplase (maximum 25mg) plus standard care versus standard care. The primary outcome is the modified Rankin scale assessed at 3 months. Other secondary outcomes will be measured at 7 days and 3 months, and collected through record linkage with national registries up to 3 years after admission.