BHF Clinical Study Grants support clinical trials and observational studies of specific patient groups, usually costing more than £350,000 or lasting more than 3 years. Previous awards have included a broad range of types and sizes of study, e.g. single centre pilot studies, large multi-centre trials, UK arms of international trials, sub-studies of ongoing trials.
April 2025
Early Atrial Fibrillation Ablation for Stroke Prevention in Patients with high Comorbidity Burden (EASThigh-UK) Conditional award*
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/22/270114)
Supported by GCRFF member funders: BHF (for recruitment in the UK), Dutch Heart Foundation (for recruitment in the Netherlands). Applications to other funders in progress (*award is conditional on sufficient additional funding being secured to support the trial in other countries).
PI: Professor G Andre Ng, University of Leicester
Award amount: £599,474 over 5 years
Grant reference: CS/F/25/190075
Proposed sample size: 325 UK participants (total sample size for international trial 2318 participants)
Recruitment planned in: Germany (lead country), UK, Australia, Canada, Czechia, Denmark, Hungary, Netherlands, Poland, Spain
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a significant health and economic burden. Patients with AF - particularly elderly patients with comorbidities - are at high risk of cardiovascular events. The EAST-AFNET4 trial demonstrated that early rhythm control of AF (with either antiarrhythmic drugs or atrial fibrillation ablation) can reduce cardiovascular events, and that attaining sinus rhythm is the key mediator of this effect. A post-hoc analysis of the trial suggested that patients with a high comorbidity burden (CHA2DS2-VASc ≥4) may derive the greatest benefit from early rhythm control. An estimated 40-65% of patients with newly diagnosed AF have a high comorbidity burden, and this patient group have been under-represented in previous AF clinical trials. The EASThigh-AFNET 11 trial will evaluate the effectiveness and safety of early AF ablation, compared to usual care, in 2318 patients with recently diagnosed AF and a high comorbidity burden (CHA2DS2-VASc ≥4). The primary outcome is a composite of cardiovascular death, stroke and hospitalisation for worsening of heart failure, at an estimated median follow-up of 44 months. Secondary outcomes include safety, health-economic outcomes, patient reported outcomes, and cognitive function. If shown to be beneficial, early AF ablation could become the default rhythm control therapy in this patient group (which comprises a large proportion of newly diagnosed AF), reducing the health and economic burden of AF and its complications.
TraNscatheter Aortic Valve Implantation vs surGical AorTic valvE Replacement in Patients with Bicuspid Aortic Valve Stenosis - NAVIGATE Bicuspid Conditional award*
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/24/270171)
Supported by GCRFF member funders: BHF (for recruitment in the UK), Dutch Heart Foundation (for recruitment in the Netherlands), German Centre for Cardiovascular Research (for recruitment in Germany), Swiss Heart Foundation (for recruitment in Switzerland). Applications to other funders in progress (*award is conditional on sufficient additional funding being secured to support the trial in other countries).
PI: Professor Daniel Blackman, University of Leeds
Award amount: £760,669 over 8 years
Grant reference: CS/F/25/190092
Proposed sample size: 200 UK participants (total sample size for international trial 1500 participants)
Recruitment planned in: Switzerland (lead country), UK, Austria, Canada, Denmark, France, Germany, Israel, Netherlands, Norway, Sweden, USA
Bicuspid aortic valve (BAV) disease is the most common congenital heart defect, with a prevalence between 0.5% and 2.0% in the general population. Compared to individuals with tricuspid aortic valve, people with BAV are at increased risk of aortic stenosis (AS) and of AS developing at a younger age. Surgical aortic valve replacement (SAVR) remains the gold standard of therapy for people with BAV and severe AS, but the emergence of transcatheter aortic valve implantation (TAVI) as an alternative to SAVR has sparked debate over the optimal treatment strategy. Given the global trend towards using TAVI for younger and lower-risk patients, there is a clear need for randomised controlled trial evidence regarding the comparative effectiveness of TAVI and SAVR in patients with BAV. NAVIGATE Bicuspid will be the first large-scale RCT to compare the efficacy and safety of transfemoral TAVI with SAVR in 1500 patients with BAV and severe AS. The trial will test whether transfemoral TAVI is non-inferior to SAVR for the primary efficacy outcome of a composite of all-cause death, stroke, or procedure-, valve- or heart failure-related re-hospitalisation at 5 years. The primary safety outcome is all-cause mortality and disabling stroke at 1 year, and secondary outcomes assessed up to 10 years will include mortality, cardiovascular events and quality of life. If TAVI is demonstrated to be non-inferior to SAVR, this research could have important benefits for patients with BAV stenosis, including avoiding surgery, shorter duration of hospitalisation for AS treatment and faster recovery of quality of life.
The Safety and Efficacy of Intravenous Thrombolysis in Patients with Ischaemic Stroke and Recent Ingestion of Direct Oral Anticoagulants - The DOAC International Thrombolysis (DO-IT) Trial
PI: Professor David Werring, University College London
Award amount: £319,691 over 3 years
Grant reference: CS/F/25/190102
Proposed sample size: 100 UK participants (total sample size for international trial 906 participants)
Recruitment planned in: Switzerland (lead country), UK, Australia, Belgium, Canada, Germany, Greece, Netherlands, Spain, Portugal, France, Japan, New Zealand, Norway
Intravenous thrombolysis (IVT) within 4.5 hours of ischaemic stroke onset is an effective treatment, that has been demonstrated to reduce disability for around 1 in 3 patients treated and to restore independence for around 1 in 7. Direct oral anticoagulants (DOACs) are the main stroke prevention option in patients with non-valvular atrial fibrillation, and around 15% of ischaemic stroke patients otherwise qualifying for IVT have a DOAC prescription. Current international guidelines recommend excluding patients with recent ingestion of DOACs (in the previous 48 hours) from receiving IVT, based on the potential risk of symptomatic intracranial haemorrhage (sICH). However, an observational international cohort study in 33,207 patients found that the rate of sICH following IVT was 2.5% in patients taking DOACs and 4.1% in those not taking DOACs, and a meta-analysis of data from previous IVT trials found no increase in sICH within 48 hours of DOAC ingestion (but was underpowered). The DO-IT trial is addressing the lack of randomised controlled trial data on the safety and efficacy of IVT in patients with acute ischaemic stroke and recent DOAC ingestion. The trial will randomise 906 participants suitable for IVT and within 48 hours of DOAC ingestion to IVT or no IVT. The primary outcome is dichotomised good functional outcome at day 90 (defined as modified Rankin Score 0-2 or return to pre-stroke baseline). Safety endpoints consist of symptomatic intracranial haemorrhage and all-cause mortality, with stopping rules at interim analyses. If IVT proves to be safe and effective in patients with recent DOAC ingestion, this will give DOAC users worldwide access to effective emergency treatment and improve quality of life when ischaemic stroke occurs.
October 2024
The Antiplatelet therapy in spontaneous coronary artery dissection Trial (APT-SCAD Trial) Conditional award*
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/21/2700127)
Supported by GCRFF member funders: BHF (for recruitment in the UK), Canadian Institutes of Health Research (for recruitment in Canada), Dutch Heart Foundation (for recruitment in the Netherlands), German Centre for Cardiovascular Research (for recruitment in Germany). Applications to other funders in progress (*award is conditional on sufficient additional funding being secured to support the trial in other countries).
PI: Professor David Adlam, University of Leicester (co-PI: Dr Rasha Al-Lamee, Imperial College London)
Award amount: £1,024,083.56 over 6 years
Grant reference: CS/F/24/190076
Proposed sample size: 500 UK participants (total sample size for international trial 3518 participants)
Recruitment planned in: Germany (lead country), UK, Australia, Canada, Denmark, India, Netherlands, New Zealand, Spain, Sweden, USA
Spontaneous coronary artery dissection (SCAD) is an increasingly recognised condition where a dissection of the coronary artery by an intramural haematoma results in myocardial ischaemia. There is currently a lack of evidence from randomised clinical trials to support treatment strategies in this group of mainly younger, female patients. Currently, patients presenting with SCAD may be treated with antiplatelet therapy (APT) developed for and mainly tested in patients with atherothrombotic disease, but the type and duration of APT to use in this group is an area of controversy. An estimated 60% of SCAD patients are discharged on dual APT (DAPT) but the use of DAPT in SCAD patients is not evidence-based. Recent registry-based studies have suggested that there may be potential harm from DAPT compared with single APT (SAPT), including increased cardiovascular and bleeding events. The APT-SCAD trial will test whether a moderate APT strategy (SAPT with aspirin for 3 months) is superior to an intensive APT strategy (3 months of DAPT with aspirin and clopidogrel, followed by 9 months of SAPT with clopidogrel) in reducing cardiovascular and bleeding events in conservatively managed SCAD patients. The trial will involve 3518 people with SCAD across multiple countries and establish vital evidence for APT use in these patients.
April 2024
Statins for venous event reduction in patients with venous thromboembolism: the SAVER trial
PI: Professor Mary Joan Macleod, University of Aberdeen
Award amount: £243,396 over 5 years, 6 months
Grant reference: CS/F/24/190065
Proposed sample size: 300 UK participants (total sample size for international trial 2700 participants)
Recruitment planned in: Canada (lead country), UK, Argentina, Brazil, France, Italy, Norway, Morocco, Saudi Arabia
Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common condition that can be fatal. Current treatment is largely limited to anticoagulation, and even with treatment people who experience VTE are at risk of recurrent VTE and secondary complications (such as post-thrombotic syndrome). Rosuvastatin is commonly prescribed for both primary and secondary prevention of arterial events such as myocardial infarction and stroke, and there some evidence that it could also be beneficial for people with VTE. SAVER is a multi-centre, randomised, double-blind placebo controlled international trial, led by researchers in Canada, that will enrol 2700 participants with recent symptomatic major VTE. Participants will be randomised to take either rosuvastatin (20 mg per day) or placebo, in addition to standard anticoagulation, for an average of 3.5 years. BHF funding for SAVER will enable 300 participants to be enrolled in the UK. The primary objective is to determine if rosuvastatin reduces the risk of recurrent VTE compared to placebo. Secondary outcomes include all-cause mortality, post thrombotic syndrome and clinically relevant bleeding. The total study duration is expected to be 5 years, with all participants being followed up for a minimum of 6 months. Demonstrating efficacy of rosuvastatin in patients with VTE could significantly reduce morbidity and mortality, improve patients’ health and quality of life, and lead to significant cost savings for the NHS.
Imaging substudy of the Antiplatelet Secondary Prevention International Randomised trial after INtracerebral haemorrhaGe (ASPIRING)
PI: Dr Grant Mair, University of Edinburgh
Award amount: £278,495 over 4 years, 8 months
Grant reference: CS/F/24/190073
Funding to enable: Collection and curation of routinely-collected brain imaging for UK participants in the ASPIRING trial
Survivors of intracerebral haemorrhage (ICH) are at risk of subsequent ischaemic cardiovascular events. However, clinicians remain concerned about secondary prevention with antiplatelet therapy in this group, because of the risk of recurrent ICH. A previous BHF-funded trial, called RESTART, found that antiplatelet therapy seemed safe for survivors of ICH, and that the antiplatelet effect on recurrent ICH may be modified by the presence of small vessel disease (SVD, the most common cause of ICH) on the brain imaging that diagnosed ICH. BHF is now funding a larger trial, called ASPIRING, which aims to provide a definitive answer as to whether antiplatelet monotherapy can reduce the risk of future major vascular events in ICH survivors. The trial will enrol ~2,743 participants in the UK, and this substudy funding is to support collection and storage of the diagnostic brain imaging (CT or MRI) scans from the UK study participants, to allow future analysis and research. Ultimately, this imaging data could help determine whether SVD modifies the effect of antiplatelet therapy on recurrent ICH, and assess whether brain imaging features could be used to personalise the safe use of antiplatelet therapy in this patient group.
October 2023
Remote screening for subclinical atrial fibrillation in elderly individuals with cardiovascular risk factors using 14-day continuous non-invasive monitoring - the Active Monitoring for Atrial Fibrillation (AMALFI) trial
PI: Professor Louise Bowman, University of Oxford
Award amount: £272,023 over 4 years
Grant reference: CS/F/23/190062
Proposed sample size: 5040 participants
Follow up of patients in: UK
Atrial fibrillation (AF) screening has been proposed as a way to prevent stroke by increasing detection of asymptomatic AF, which might be missed in usual care. Opportunistic screening (e.g. pulse-palpation/12-lead ECG) during healthcare consultations is recommended by some clinical practice guidelines. However, international taskforces do not recommend systematic AF screening, citing the uncertainty regarding both clinical utility and cost-effectiveness. The AMALFI trial will examine whether AF screening in people aged 65+ with cardiovascular risk factors, using mail-based 14-day ECG monitoring (ZioPatch, iRhythm), leads to increased and earlier AF detection over 5 years. AMALFI has completed recruitment (n=5040), with 85% adherence to the intervention and AF detection rates consistent with sample size estimates. BHF funding will support follow-up via GP records and NHS England datasets. If found to improve long-term AF detection cost-effectively, this streamlined and pragmatic design could be scaled up to form the basis of a future nationwide AF screening program.
The United Kingdom Metformin Aneurysm Trial (UKMAT)
PI: Professor Matthew Bown, University of Leicester
Award amount: £1,290,726 over 5 years
Grant reference: CS/F/23/190063
Proposed sample size: 1000 UK participants (total sample size for international trial 2000 participants)
Recruitment planned in: Australia (lead country), UK and New Zealand
Abdominal aortic aneurysms (AAA) are responsible for over 4000 deaths per annum in the UK, and over 4000 people have surgery to prevent AAA rupture. AAAs are usually identified through population screening programmes or incidentally. Most AAA are small when diagnosed and pose no immediate risk of rupture. The mainstay of management for small AAAs is longitudinal monitoring until aneurysm size reaches the point at which the risk of rupture exceeds the risk of repair. People with small AAA usually spend many years in AAA surveillance programmes before they are considered for surgery. This period represents an opportunity to intervene to prevent AAA growth, and therefore reduce the need for surgery. However, there are currently no proven treatments to prevent AAA growth. Several observational studies have shown that people with diabetes and AAA who are taking metformin have slower AAA growth than those on other agents. The international Metformin Aneurysm Trial, of which UKMAT will be a part, is a phase IIIb double-blind, placebo-controlled randomised clinical trial of metformin (1500mg/day) in people with small (35-49mm) AAA. The primary outcome will be the combined incidence of AAA repair (open or endovascular) or mortality due to AAA rupture. If positive, the trial will identify the first ever treatment to prevent the progression of AAA in humans.
10-year median follow-up of long-term stroke onset rates in ACST-2, the largest randomised trial of carotid surgery vs carotid stenting
PI: Mr Richard Bulbulia, University of Oxford
Award amount: £341,412 over 3 years
Grant reference: CS/F/23/190067
Proposed sample size: ~2600 participants for 10 year median follow up
Follow up of patients in: 30 countries (including UK).
Each year, around 500,000 patients across the world undergo carotid endarterectomy (CEA) or carotid artery stenting (CAS) for symptomatic or asymptomatic carotid artery stenosis. Both procedures carry an immediate risk of peri-procedural stroke, after which both reduce the stroke onset rate to ~1% per year. However, there is currently no evidence from randomised controlled trials comparing the long-term (5-10+ year) durability of protection against stroke after these two procedures. ACST-2 is a large, multinational trial that randomised 3625 patients with asymptomatic carotid artery stenosis to CEA or CAS between 2008 and 2021. After a mean of 5 years of follow-up, the rates of peri-procedural and non-procedural disabling or fatal stroke were similar between the groups. Follow up will now be extended (up to a median of 10 years) to determine whether there is a difference in long-term restenosis and stroke rates between the procedures. Demonstrating equivalence up to 10 years would help give clinicians and patients a freer choice between CEA and the less invasive CAS procedure. Alternatively, demonstrating a difference in long-term restenosis and stroke rates between CEA and CAS could influence guidelines and practice for patients with asymptomatic or symptomatic carotid artery stenosis.
April 2023
Randomized comparison of the Outcomes of single vs Multiple Arterial grafts trial in Women (ROMA-Women)
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/21/270098)
Supported by GCRFF member funders: BHF (for recruitment in the UK), Canadian Institutes of Health Research (for recruitment in Canada), Dutch Heart Foundation (for recruitment in the Netherlands), German Centre for Cardiovascular Research (for recruitment in Germany). Applications to other funders in progress.
PI: Professor Gavin Murphy, University of Leicester
Award amount: £311,191 over 6 years, 6 months
Grant reference: CS/F/22/190055
Proposed sample size: 216 UK participants (total sample size for international trial 2000 participants)
Recruitment planned in: USA (lead country), UK, Australia, Austria, Canada, Germany, Sweden, The Netherlands
Coronary artery bypass grafting (CABG) is the most commonly performed adult cardiac surgery procedure worldwide. The long-term success of CABG is determined by graft patency, and arterial bypass grafts have superior long-term patency to vein grafts. However it is currently unclear whether using multiple arterial grafts (MAG) in people undergoing CABG results in better long-term outcomes versus a single arterial graft plus vein grafts (SAG), as the results of previous randomised trials in this area do not consistently favour MAG over SAG. This uncertainty is greater in women as these trials predominantly recruited men, and there is evidence that MAG treatment effects may be different between sexes. Leveraging the existing infrastructure of the ongoing ROMA trial, ROMA-Women will be the first cardiac surgery trial to exclusively enrol women. This multinational clinical trial will involve 2000 women of any age undergoing non-emergency CABG, who will be randomised 1:1 to MAG or SAG. The primary outcome is a composite of death from any cause, stroke, myocardial infarction occurring >48 hours after surgery, repeat revascularisation, or rehospitalisation for heart failure or acute coronary syndrome. If positive, the results will change existing treatment guidelines, increase the use of MAG, and improve clinical and patient-reported outcomes in women undergoing CABG.
Women's Aneurysm Research: Repair Immediately Or Routine Surveillance: WARRIORS trial: Conditional award*
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/21/270099)
Supported by GCRFF member funders: BHF (for international co-ordination and recruitment in the UK), Dutch Heart Foundation (for recruitment in the Netherlands). Applications to other funders in progress (*award is conditional on sufficient additional funding being secured to support the trial in other countries).
PI: Mr Colin Bicknell, Imperial College London (co-PI: Miss Anna Louise Pouncey, Imperial College London)
Award amount: £2,257,539 over 9 years, 6 months
Grant reference: CS/F/22/190056
Proposed sample size: 150 UK participants (total sample size for international trial 1112 participants)
Recruitment planned in: UK (lead country), Australia, Canada, Denmark, Finland, France, Germany, Italy, New Zealand, Portugal, Sweden, The Netherlands, USA
Elective Abdominal Aortic Aneurysm (AAA) repair is offered when the risk of rupture exceeds the risk of surgery, typically at a threshold of 5.5cm in diameter. Women (versus men) have a four-fold higher risk of AAA rupture, but almost double the operative mortality. It is unknown whether the current 5.5cm AAA repair threshold, derived from randomised trials including only 4% women, is applicable to women. A key question is whether women should have their aneurysms repaired electively at smaller diameters than men to improve their AAA-related survival and quality of life. WARRIORS is an international randomised controlled trial of early elective endovascular repair versus routine surveillance in women (n=1112) with small asymptomatic AAA (4-5.4cm diameter), nested within a registry of non-participants. The surveillance group will be offered repair for rupture or upon reaching the 5.5cm threshold. Randomisation will be 1:1 stratified by country, age, and aneurysm diameter. The trial is powered for primary outcome of aneurysm-related mortality or rupture at 5 years and Quality-Adjusted-Life-Years (QALYs) as a key secondary outcome. Other outcomes include operative mortality and complications, anxiety and cost-effectiveness. The trial aims to progress health equity through provision of evidence for sex-specific clinical guidelines for AAA repair.
October 2022
Antiplatelet Secondary Prevention International Randomised trial after INtracerebral haemorrhaGe (ASPIRING): a pragmatic, randomised, parallel group, open, superiority, phase 3 multinational clinical trial
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/21/270024)
Supported by GCRFF member funders: BHF (for international co-ordination and recruitment in the UK), Canadian Institutes of Health Research (for recruitment in Canada) and Dutch Heart Foundation (for recruitment in the Netherlands).
PI: Professor Rustam Salman, University of Edinburgh
Award amount: £2,333,936 over 6 years
Grant reference: CS/F/22/190053
Proposed sample size: 2828 UK participants (total sample size for international trial 4148)
Recruitment planned in: UK (lead country), Australia, Belgium, Canada, The Netherlands
Non-traumatic intracerebral haemorrhage (ICH) is estimated to account for 54% of years of life lost due to stroke worldwide, and survivors are at 7-19% annual risk of further major adverse cardiovascular events (MACE). A previous BHF-funded clinical trial (RESTART) showed that, in UK-based ICH survivors with symptomatic occlusive vascular disease, starting antiplatelet therapy was safe and may have reduced the risk of MACE. Building on these findings, the ASPIRING trial aims to provide a definitive answer as to whether antiplatelet monotherapy can reduce the risk of future major vascular events in ICH survivors. The trial will recruit ~4148 adult participants who survive ≥24 hours after symptomatic ICH, and have not started antiplatelet or anticoagulant drug therapy after ICH, from around 178 hospitals worldwide. Participants will be randomised to start or avoid antiplatelet monotherapy, and will be followed up for up to 5 years. The primary outcome will be a composite of ischaemic and haemorrhagic MACE (non-fatal stroke, non-fatal myocardial infarction, or vascular death). Conducting ASPIRING on an international scale will help to recruit the target number of participants in a timely fashion, enhance the generalisability of the results, and allow investigation of heterogeneity in treatment effects across important sub-groups (e.g., time since ICH, sex and ethnicity). The results will inform clinical guidelines and, if the intervention is shown to be beneficial, could lead to improved outcomes in an under-served patient population.
Low dose ColchicinE in pAtients with peripheral artery DiseasE to address residual vascular Risk: A randomized trial (LEADER-PAD Trial)
Trial endorsed by the GCRFF Multinational Clinical Trials Initiative (Reference: GCRFF/21/270035)
Supported by GCRFF members funders: BHF (for UK recruitment), Canadian Institutes of Health Research (for international co-ordination and recruitment in Canada, Ecuador, Argentina, India, Belgium, Italy, Brazil), National Heart Lung and Blood Institute (for recruitment in the United States of America).
PI: Professor Robert Hinchliffe, University of Bristol
Award amount: £1,405,301 over 4 years, 9 months
Grant reference: CS/F/22/190051
Proposed sample size: 1500 UK participants (total sample size for international trial 6150 participants)
Recruitment planned in: Canada (lead country), UK, Argentina, Australia, Belgium, Brazil, Ecuador, India, Italy, Singapore, The Netherlands, USA
People with chronic peripheral arterial disease (PAD) have a high lifetime vascular risk, despite current preventative therapies (e.g., statins, anti-coagulation). Compared to people with coronary or cerebrovascular disease, they are more likely to have extensive atherosclerosis (≥2 vascular beds affected) and experience vascular complications. There is growing evidence from trials in patients with coronary artery disease (LoDoCo; COLCOT) that colchicine - a low-cost, readily available drug that has been shown to inhibit inflammatory pathways involved in atherosclerosis – can help to prevent atherothrombosis, but this has not yet been explored in patients with PAD. LEADER-PAD is a placebo-controlled, multinational clinical trial testing whether low-dose (0.5mg/day) colchicine can reduce the incidence of major adverse cardiovascular and limb events in patients with PAD. The trial will recruit 6150 participants with symptomatic lower extremity PAD, including 1500 participants from 20 hospitals in the UK. Following a 2-week active run-in phase, participants will be randomised to colchicine or placebo and followed up every 6 months after enrolment, for a minimum of 12 months. The primary outcome will be the rate of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke) and major adverse limb events (MALE: acute limb ischaemia, major amputation). If LEADER-PAD demonstrates that colchicine is safe and effective at preventing vascular events in people with PAD, it could mean that this low cost, readily available drug could form part of routine treatment for this group.
April 2022
Using cardiovascular magnetic resonance identified scar as the Benchmark Risk Indication Tool for Implantable cardioverter defibrillators in patients with Non-Ischaemic Cardiomyopathy and Severe systolic Heart failure (BRITISH)
PI: Dr Andrew Flett, University of Southampton
Award amount: £1,689,637 over 6 years, 5 months
Grant reference: CS/F/21/190049
Proposed sample size: 1252 participants
Recruitment planned in: UK
Sudden arrhythmic death is an important cause of death in patients with non-ischaemic cardiomyopathy (NICM). Current guidelines recommend prophylactic implantation of a defibrillator (ICD) if left ventricular ejection fraction (LVEF) is ≤35%. However a recent substantial trial (DANISH) found no overall benefit from an ICD in this population. Strategies to improve stratification of NICM patients who would benefit from an ICD could therefore have important clinical and economic impacts. The BRITISH trial aims to determine whether the presence of heart scarring - detected by cardiac MRI scanning (CMR) - may be a better stratifier for the use of ICDs in NICM patients. The trial will enrol 1252 patients with NICM and CMR-detected heart scar who will be randomly assigned to receive either an ICD or an implantable loop recorder (ILR). Participants will be followed up for 3 years after they receive an ICD or ILR, and will also be asked for consent to track their electronic health records for up to 10 years. The primary outcome will be all-cause mortality after 3 years. A registry will allow observation of event rates in scar negative NICM patients. The results of this trial will help inform international guidelines in this area, and have the potential to improve care for people with NICM.
Cryoballoon/Radiofrequency/Pulsed Field Ablation of atrial fibrillation versus medical treatment for heart failure: CRAAFT-HF
PI: Professor Pier Lambiase, University College London
Award amount: £1,576,568 over 6 years, 2 months
Grant reference: CS/F/21/190034
Proposed sample size: 1200 participants
Recruitment planned in: UK, Australia, Sweden
An estimated 900,000 people in the UK are living with heart failure, and it's thought that around 40% of these individuals also have atrial fibrillation (AF). Having heart failure and AF together can worsen both conditions, and is linked to having more severe heart failure and higher mortality. AF can be treated using catheter ablation, using a cryo-balloon, radio-frequency or pulsed field ablation pulmonary vein isolation (PVI) technique. Numerous small studies have shown that restoration of sinus rhythm by catheter ablation in patients with heart failure and AF improves left ventricular function and exercise tolerance. One small trial (CASTLE-AF, n=363) in heart failure patients with an ICD or CRT device reported reduced mortality in the group receiving AF ablation, but there is a need to assess this potential mortality benefit in a general heart failure population. CRAAFT-HF is a randomised, open label multi-centre clinical trial which will enrol 1200 participants with heart failure with reduced ejection fraction (<50%) and="" paroxysmal="" or="" persistent="" af.="" participants="" will="" be="" randomised="" to="" receive="" pvi="" and="" medical="" af="" therapy="" or="" medical="" af="" therapy="" alone,="" and="" will="" also="" receive="" the="" best="" possible="" heart="" failure="" treatments.="" participants="" will="" be="" followed="" up="" for="" up="" to="" 4="" years="" to="" assess="" whether="" pvi="" reduces="" mortality="" and="" hospitalisations="" in="" people="" living="" with="" both="" heart="" failure="" and="" af,="" while="" also="" assessing="" impact="" quality="" of="">
October 2021
PROTECT-HF: Physiological Vs Right ventricular pacing Outcome Trial Evaluated for bradyCardia Treatment
PI: Dr Zachary Whinnett, Imperial College London
Award amount: £1,689,637 over 6 years, 6 months
Grant reference: CS/F/21/190036
Proposed sample size: 2600 participants
Recruitment planned in: UK, Belgium, Italy, Norway, Poland, Switzerland, USA
Each year in the UK, around 40,000 people need a pacemaker for bradycardia. Right ventricular (RV) pacing is a life-saving treatment for bradycardia, but pacing the heart in this way produces abnormal ventricular activation patterns. In the long term, this can cause left ventricular (LV) dysfunction, and consequent mortality and heart failure morbidity. Physiological pacing is an alternative pacing method, which involves carefully positioning a pacing lead to directly stimulate the highly specialised His-Purkinje fibres (His bundle or left bundle) - thereby achieving a more normal ventricular activation pattern. Previous observational studies have shown that physiological pacing is technically feasible and clinically safe, and suggest better long-term preservation of LV function and lower risk of death and heart failure. However, there is a lack of randomised clinical trial evidence to support this. The PROTECT-HF trial will enrol 2600 patients with a bradycardia indication for pacing and ejection fraction >35%, who will be randomised to receive either RV or physiological pacing (His bundle or left bundle pacing at the operator's discretion). With a median 4 years of follow-up, death and heart failure will be assessed as the primary endpoint, and blinded heart failure symptoms as an important secondary endpoint. This landmark trial aims to definitively establish whether physiological pacing (which has no extra device cost) can help protect patients receiving anti-bradycardia pacing from long-term mortality and morbidity.
April 2021
Best Endovenous treatment, including STenting, versus best non-endovenous treatment in chronic proximal deep venous disease – the BEST multi-centre randomised controlled trial
PI: Professor Alun Davies, Imperial College London
Award amount: £737,451 over 4 years
Grant reference: CS/F/21/190038
Proposed sample size: 328 participants
Recruitment planned in: UK, Ireland
Chronic obstruction of the iliac veins or inferior vena cava can occur as a result of deep vein thrombosis (DVT), or due to extrinsic compression in non-thrombotic iliac vein lesions (NIVLs). This obstruction can manifest as post-thrombotic syndrome (PTS) after DVT or as chronic venous disease in NIVL. Despite sparse evidence, rates of venous stenting for PTS and NIVL are increasing. The BEST trial is a pragmatic, observer-blind, multicentre, randomised controlled trial in adults with chronic venous disease secondary to either PTS or NIVL. Participants will be randomised to either best endovenous therapy (including venoplasty and deep venous stenting) or standard therapy (compression +/- anticoagulation). Included participants will have chronic venous disease (CEAP classification 3–6) secondary to proximal deep venous disease. The primary outcome is severity of venous disease at 6 months as ascertained by the Venous Clinical Severity Score (VCSS). The BEST trial will be the first of its kind to provide high quality level I evidence in the context of the use of endovenous reconstruction in PTS and NIVL, determining the clinical and cost effectiveness of best endovenous reconstruction with dedicated venous stents in a European population. If there is no clinical benefit for endovenous stenting, it has the potential to prevent patients undergoing a non-beneficial intervention. If clinically beneficial and cost effective, this will represent a clear indication to expand services for patient benefit.
Randomised trial of bilateral versus single internal thoracic artery graft surgery follow up to 15 years: the Arterial Revascularisation Trial (ART)
PI: Professor David Taggart, University of Oxford
Award amount: £148,514 over 1 year
Grant reference: CS/F/21/190041
Proposed sample size: ~2387 participants for 15 year follow up
Follow up of patients in: UK, Australia, Austria, Brazil, India, Italy, Poland
The superior patency of arterial grafts over vein grafts for coronary artery bypass grafting (CABG) is well established, and leads to significantly improved survival as well as reduced risk of further myocardial infarction and the need for repeat revascularisation. The Arterial Revascularization Trial (ART), conducted from 2004 to 2007, investigated whether the addition of a second internal thoracic artery graft would further reduce mortality, myocardial infarction and repeat revascularisation in people post CABG. Patients scheduled for CABG were randomly assigned to undergo either bilateral or single internal-thoracic-artery grafting. ART is the largest trial of an intervention in people with severe coronary artery disease, with over 3,000 participants already followed for 10 years. At 10 years there was no difference in mortality, but there was emergence of a reduction in the composite end point after 8 years (but which did not reach statistical significance by 10 years). At 10 years 80% of the ART cohort are still alive and following the participants to 15 years will provide important information on the ‘natural history’ of CABG and may also reveal clinically significant differences because of the continuing attrition of vein grafts between 10 and 15 years. If so, this will be of major clinical relevance in guiding the optimal surgical strategy in CABG and particularly for younger patients who have a much longer life expectancy.
October 2020
Multi-centre open label randomised controlled trial of immediate 14 day ambulatory ECG monitoring versus standard care in acute unexplained syncope patients: The ASPIRED study
PI: Dr Matthew Reed, University of Edinburgh
Award amount: £1,303,649 over 4 years
Grant reference: CS/F/21/190016
Proposed sample size: 2234 participants
Recruitment planned in: UK, Ireland
Diagnosing underlying dysrhythmia in people presenting to the emergency department is difficult. There is evidence that the diagnostic yield for detecting underlying dysrhythmia is highest when cardiac monitoring devices are applied early in patients with acute unexplained syncope, ideally at the index visit. The ASPIRED study is an open label, prospective parallel group multicentre randomised controlled trial of an immediate 14-day ambulatory heart patch monitor versus standard care (Holter/extended ambulatory monitor as per NICE guidance) in over 2000 people presenting acutely with unexplained syncope. The primary endpoint will be the number of episodes of syncope at one year. Secondary end points include cost effectiveness, the number of episodes of syncope at 90 days and 2 years, clinically significant cardiac dysrhythmia, all cause death and quality of life.
REducing Microvascular dysfunction in patients with angina, ischaemia and unobstructED coronarY arteries – a pilot study (REMEDY-Pilot)
PI: Dr Pettahandige de Silva, Imperial College London
Award amount: £287,287 over 3 years
Grant reference: CS/F/20/35120
Proposed sample size: 54 participants
Recruitment planned in: UK (single centre pilot study)
Symptomatic angina and myocardial ischaemia in people without evidence of obstructive epicardial coronary artery disease is called ischaemia with normal coronary arteries (INOCA) and is associated with an increased rate of adverse cardiovascular events and poor quality of life. In many of these patients, ischaemia is caused by coronary microvascular dysfunction (cMVD). Current treatments, predominantly pharmacological, have little evidence base and are of limited efficacy. The coronary sinus reducer (CSR) is a new treatment for refractory angina, which creates a focal narrowing in the coronary sinus that increases back pressure and redistributes blood into ischaemic myocardium at the level of the microcirculation. It is proposed that the CSR is a biologically plausible intervention that may improve symptoms in patients with INOCA and cMVD who continue to experience angina refractory to conventional treatment. The REMEDY-Pilot study is a randomised double-blind sham-controlled pilot study to confirm acceptability of CSR implantation, demonstrate feasibility to recruit and quantify its effect on myocardial perfusion. Secondary patient-related outcomes will include angina severity and quality of life. Results from REMEDY-Pilot will inform the design and conduct of a study powered for clinical efficacy.
A prospective randomised trial comparing radiofrequency ablation With laparoscopic Adrenalectomy as an alternatiVE treatment for unilateral primary aldosteronism (WAVE)
PI: Professor Morris Brown, Queen Mary, University of London
Award amount: £497,884 over 4 years
Grant reference: CS/F/20/190025
Proposed sample size: 110
Recruitment planned in: UK
Of the 12 million people in the UK with hypertension, 5-10% have primary aldosteronism (PA). Cardiac morbidity (atrial fibrillation, heart failure) in people with PA is twice that in essential hypertension; this combination of prevalence and penalty mandates detection, investigation and treatment of PA. Around 50% of cases are caused by a single, potentially resectable aldosterone producing adenoma (APA), but at present, less than 1% of cases are investigated and treated. The reasons include surgical capacity, uncertain surgical outcomes, and physician/patient reluctance to recommend/undergo resection of an entire gland as treatment for a small, benign tumour. Retrospective reports of radiofrequency ablation (RFA) or APAs suggest a promising solution to these issues. WAVE is a prospective, randomised, open-label with blind endpoint, multicentre clinical trial comparing RFA versus laparoscopic adrenalectomy (LA) for the treatment of APA. It will establish, in 110 patients with PA and a unilateral APA, whether RFA is non-inferior to LA in curing biochemical PA and hypertension, and superior in measures of morbidity and time-off-work. The results of WAVE could transform management of PA, and substantially improve outcomes in a large number of hypertensive patients.
October 2019
British Heart Foundation randomised clinical trial of cerebral embolic protection in transcatheter aortic valve implantation (BHF PROTECT-TAVI)
PI: Professor Rajesh Kharbanda, University of Oxford
Award amount: £2,251,003 over 6 years
Grant reference: CS/20/1/34732
Proposed sample size: 7730 participants
Recruitment planned in: UK
Aortic stenosis is treated by transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (AVR). TAVI is less invasive, has less morbidity and allows faster recovery than surgical AVR. However, a major risk of TAVI is stroke, which occurs in about 3% of TAVI patients, and is associated with prolonged hospital stay, disability and earlier death. Most strokes occur at the time of TAVI due to embolism of debris released from the native valve and surrounding anatomy into the cerebral circulation. It is thought that cerebral embolic protection (CEP) devices could reduce the chances of debris reaching the brain and that these devices may reduce stroke. The BHF PROTECT-TAVI trial will investigate whether CEP devices reduce the likelihood of stroke during TAVI. 7730 people having transfemoral TAVI for aortic stenosis will be recruited from across the UK. Half of the participants will be randomised to have TAVI performed with CEP. The control group will have standard of care for TAVI without CEP. The primary outcome will be clinical stroke at 72 hours. BHF PROTECT-TAVI will define the clinical effectiveness of CEP to reduce stroke. A cost-effectiveness analysis to inform NHS decision-making will also be undertaken.
Del Nido versus St Thomas’ blood cardioplegia: A multi-centre randomised controlled trial in children undergoing cardiac surgery
PI: Mr Nigel Drury, University of Birmingham
Award amount: £566,211 over 3 years
Grant reference: CS/20/3/34738
Proposed sample size: 220 participants
Recruitment planned in: UK
Cardioplegia is fundamental to the surgical repair of congenital heart defects by protecting the heart against ischaemia-reperfusion injury. The immature myocardium is different to the adult, and there is limited evidence to support one cardioplegia solution over another. Whereas St Thomas’ cardioplegia is the most widely used solution in the UK, del Nido solution was specifically designed in the US to protect the immature heart and may provide better myocardial protection in children. This pilot study aims to find out whether del Nido cardioplegia reduces myocardial injury in the early postoperative period compared with St Thomas’ blood cardioplegia. 220 children undergoing surgery at 4 UK centres will be recruited into the study. They will be randomised to receive either del Nido or St Thomas’ cardioplegia solution, and troponin release after surgery will be measured to assess myocardial injury. The trial will provide information on whether either cardioplegic solution may be superior in children and support the need for a definitive trial in children of different ages to assess clinical outcomes.
Aldosterone blockade for health improvement evaluation in end-stage renal disease. Proposal for a randomised double-blind placebo-controlled trial in the United Kingdom (ACHIEVE-UK)
PI: Professor Patrick Mark, University of Glasgow
Award amount: £650,557 over 4 years, 8 months
Grant reference: CS/20/2/34731
Proposed sample size: 600 UK participants (total sample size of 2750 internationally)
Recruitment planned in: UK (international trial recruiting in Australia, Brazil, Canada, Ecuador, India, Malaysia, New Zealand, Philippines, Uruguay)
Patients with end stage renal disease (ESRD) requiring dialysis are at high risk of cardiovascular death and heart failure, at least 7-fold higher than age matched controls. The most common cause of cardiovascular death is a combination of sudden cardiac death and heart failure rather than atherosclerotic events. Aldosterone is elevated in ESRD and promotes cardiac damage. Mineralocorticoid receptor antagonism (MRA) with spironolactone has been shown to improve survival in patients with heart failure, who show similarities to ESRD. Pilot clinical trials show that MRA is safe in ESRD and is associated with improvements in surrogate cardiovascular end points such as carotid intima medial thickness. The ACHIEVE trial is an international randomised controlled trial, led from McMasters University in Canada, which aims to assess if spironolactone reduces cardiovascular mortality or heart failure in ESRD. The global trial will recruit 2750 people with ESRD having dialysis, ACHIEVE-UK will contribute 600 participants to the international trial, from 24 hospitals across the UK. The primary outcome will be a composite of cardiac death or hospitalisation at 3 year follow up.
November 2018
The TIGHT-K STUDY. Arrhythmias on the cardiac intensive care unit - does maintenance of high-normal serum potassium levels matter?
PI: Dr Benjamin O'Brien, Queen Mary, University of London
Award amount: £1,200,000 over 4 years, 6 months
Grant reference: CS/18/3/34063
Proposed sample size:1684 participants
Recruitment planned in: UK, Germany
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
PI: Professor David Newby, University of Edinburgh
Award amount: £943,260 over 8 years
Grant reference: CS/18/4/34074
Proposed sample size: 6000 participants
Recruitment planned in: UK
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)
PI: Professor Keith Muir, University of Glasgow
Award amount: £488,647 over 4 years
Grant reference: CS/18/5/34081
Proposed sample size: 300 UK participants (total sample size of 1274 internationally)
Recruitment planned in: UK (international trial recruiting in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain)
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
PI: Professor Keith Muir, University of Glasgow
Award amount: £551,803 over 2 years, 6 months
Grant reference: CS/18/6/34079
Proposed sample size: 400 participants
Recruitment planned in: UK
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
PI: Professor Gerry McCann, University of Leicester
Award amount: £2,722,054 over 10 years
Grant reference: CS/18/7/33714
Proposed sample size: 2844 participants (across all participating countries)
Recruitment planned in: UK (international trial recruiting in Australia, New Zealand)
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 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, Australia and New Zealand. 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)
PI: Professor Nicholas Mills, University of Edinburgh
Award amount: £1,115,723 over 5 years
Grant reference: CS/18/1/33711
Proposed sample size: 2270 participants
Recruitment planned in: UK
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 multicentre 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
PI: Professor Rustam Al-Shahi Salman, University of Edinburgh
Award amount: £721,223 over 3 years
Grant reference: CS/18/2/33719
Proposed sample size: 190 participants
Recruitment planned in: UK
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
PI: Professor David Werring, University College London
Award amount: £2,045,998 over 5 years
Grant reference: CS/17/6/33361
Proposed sample size: 3474 participants
Recruitment planned in: UK
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
PI: Dr Roy Gardner, University of Glasgow
Award amount: £429,737 over 4 years, 6 months
Grant reference: CS/17/4/33009
Proposed sample size: 500 participants
Recruitment planned in: UK
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)
PI: Professor Thompson Robinson, University of Leicester
Award amount: £323,014 over 3 years
Grant reference: CS/17/5/32826
Proposed sample size: 200 UK participants (total sample size of 500 internationally)
Recruitment planned in: UK (international trial recruiting in Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, USA)
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.