Active GCRFF trials

Trials endorsed by the GCRFF Multinational Clinical Trials Initiative 

  • ASPIRING - Antiplatelet Secondary Prevention International Randomised trial after INtracerebral haemorrhaGe 

  • LEADER-PAD - Low dose ColchicinE in pAtients with peripheral artery DiseasE to address residual vascular Risk 

  • CONTEMP-ICD - The Comparative Effectiveness of Contemporary Heart Failure Medical Management With vs. Without an ICD 

  • ROMA-Women - Randomized comparison of the Outcomes of single vs Multiple Arterial grafts trial in Women 

ASPIRING - Antiplatelet Secondary Prevention International Randomised trial after INtracerebral haemorrhaGe

Led by Professor Rustam Salman, University of Edinburgh (UK)

A picture of the world, highlighting the locations of the participating groups.

Endorsed November 2021 

EOI reference: GCRFF/21/270024 
Total sample size: 4148 participants 
Estimated total cost: £4.3m 
Trial registration: ISRCTN16705062

Recruitment planned in: 

UK (2828 participants), Canada (450 participants), The Netherlands (356 participants), Australia (330 participants), Belgium (240 parictipants) 

Supported by: 

BHF (international co-ordination and recruitment in the UK), Canadian Institutes of Health Research (recruitment in Canada), Dutch Heart Foundation (recruitment in the Netherlands), Medical Research Futures Fund (recruitment in Australia), The Research Foundation Flanders (recruitment in Belgium) 

An intracerebral haemorrhage (or ICH) is a type of stroke caused by bleeding into the brain. People who survive an ICH are at an increased risk of experiencing another major vascular event (such as a heart attack, stroke, or dying due to a clotting or bleeding problem) in the future. Antiplatelet drugs, such as aspirin, help to prevent dangerous blood clots and are widely used to help prevent heart attacks and strokes in people at high risk. Currently, people who have experienced an ICH are usually kept off drugs that prevent clotting because of the potential risk of further bleeding into the brain. However, a previous clinical trial called RESTART showed that taking antiplatelet drugs after an ICH seemed to be safe, and might even help to prevent major vascular events, such as heart attacks or strokes caused by a blood clot. Building on these findings, the team behind RESTART are now leading a larger, international clinical trial called ASPIRING. ASPIRING will involve 4148 people who have experienced an ICH, who will be recruited from hospitals across the UK and at least four other countries worldwide. Participants will be randomly assigned to either start or avoid taking an antiplatelet drug - this can be aspirin, clopidogrel, dipyridamole, cilostazol, ticagrelor or ticlopidine - depending on what their doctor thinks is best for them. They will be followed up for up to 5 years to find out whether there is a difference in the number of major vascular events between the two groups. If taking an antiplatelet is found to be beneficial, this could help improve outcomes for the quarter of a million ICH survivors worldwide each year. 

LEADER-PAD - Low dose ColchicinE in pAtients with peripheral artery DiseasE to address residual vascular Risk 

Led by Dr Noel Chan, McMaster University (Canada) 

A picture of the world, highlighting the locations of the participating groups.

Endorsed November 2021 

EOI reference: GCRFF/21/270035 
Total sample size: 6150 participants 
Estimated total cost: £11.3m 
Trial registration: NCT04774159 

Recruitment planned in: 

Canada, Ecuador, Argentina, India, Belgium, Italy, Brazil (3000 participants), UK (1500 participants), The Netherlands (1500 participants), United States of America (1000 participants) 

Supported by funders: 

Canadian Institutes of Health Research (for international co-ordination and recruitment in Canada, Ecuador, Argentina, India, Belgium, Italy, Brazil), British Heart Foundation (recruitment in the UK), ZonMw (recruitment in the Netherlands), National Heart, Lung, and Blood Institute (recruitment in the USA) 

Peripheral arterial disease (PAD) happens when the arteries supplying blood to the arms or legs become narrowed. It is usually caused by inflammation and fatty build up in the walls of the arteries (atherosclerosis), meaning less blood can get through, similar to the blockage of blood vessels supplying the heart in people with coronary artery disease (CAD). PAD usually effects the legs, and can often lead to leg pain and, in severe cases, gangrene and even amputation. People with PAD are also at high risk of other cardiovascular complications, such as a heart attack or stroke, even if they are treated with existing preventive medications (such as anti-clotting drugs or statins). Colchicine is an anti-inflammatory medication commonly used to treat gout. Previous research has shown that a low dose of colchicine could help to reduce heart attacks, stroke and other cardiovascular complications for people with CAD. As PAD has the same underlying cause as CAD, an international team of researchers want to find out whether colchicine could help people living with PAD too. The LEADER-PAD trial will involve 6150 participants with PAD worldwide. All participants will take colchicine for a two week ‘run in’ period, to make sure that they are able to safely take the drug (as it can have side effects, such as digestive symptoms). After run-in, they will be randomly assigned to take either a low dose of colchicine (0.5mg per day) or an identical placebo tablet that doesn’t have any drug in it. They will attend hospital for follow up visits every 6 months for up to 3 years to find out whether there is a difference in the number of major vascular or limb events between the two groups (including dying due to a cardiovascular cause, heart attack, stroke, and severe clotting in a limb – including needing an amputation). If the results of LEADER-PAD show that taking colchicine is beneficial, the drug would be a new treatment for a group of patients who do not currently have many effective medications available. As colchicine is a cheap drug, which is already safely used for other conditions, this would also mean it could be rolled out more quickly as a new treatment option worldwide. 

CONTEMP-ICD - The Comparative Effectiveness of Contemporary Heart Failure Medical Management With vs. Without an ICD

Led by Dr Ilan Goldenberg, University of Rochester (USA) 

A picture of the world, highlighting the locations of the participating groups.

Endorsed November 2021 

EOI reference: GCRFF/21/270056 
Total sample size: 3290 participants 
Estimated total cost: ~$27m (USD) 
Trial registration: NCT06543446 

Recruitment planned in: 

USA, Canada (up to 3290 participants), Slovenia (200 participants) 

Supported by: 

Patient-Centred Outcomes Research Institute (recruitment in US and Canada) 

Some people with heart failure are at risk of experiencing fast, dangerous heart rhythms. An ICD is a device that is implanted under the skin in the chest to monitor the heartbeat, and if a dangerous rhythm is detected, deliver an electric shock to try and restore a normal heart rhythm. ICDs can be lifesaving, but many people who receive an ICD will never need it to deliver a shock, and having an ICD has some risks (such as infections or shocks being given inappropriately). Also, the current guidelines on recommending ICDs are mostly based on trials that happened before many newer heart failure medications were available. This has called into question whether people with heart failure, who have not experienced a life-threatening heart rhythm problem in the past, should be offered an ICD. The CONTEMP-ICD trial aims to enrol 3290 people with heart failure, who are eligible to have an ICD under the current guidelines, but have been assessed as being at low risk of needing an ICD shock using a clinical scoring system. Participants will be randomly assigned to either receive an ICD or not. All participants will be given recommended heart failure medication. They will be followed up for up to 4 years to assess whether there is any difference in outcomes between the two groups (including risk of dying, experiencing a ‘cardiovascular event’ such as a heart attack or stroke, and ICD complications such as inappropriate shocks). The results of CONTEMP-ICD will provide vital information on whether the guidelines on ICD should be adjusted in light of advances in heart failure medications.  

ROMA-Women - Randomized comparison of the Outcomes of single vs Multiple Arterial grafts trial in Women 

Led by Dr Mario Gaudino, Weill Cornell Medicine (USA) 

A picture of the world, highlighting the locations of the participating groups.

Endorsed November 2021 

EOI reference: GCRFF/21/270098 
Total sample size: 2000 participants 
Estimated total cost: ~£6.2m 
Trial registration: NCT04124120 

Recruitment planned in: 

USA (812 participants), Canada (130 participants), UK (216 participants), Germany (170 participants), Austria (90 participants), The Netherlands (250 participants) 

Supported by: 

Canadian Institutes of Health Research (recruitment in Canada), British Heart Foundation (recruitment in the UK), DZHK (recruitment in Germany), Austrian Science Fund (recruitment in Austria), Starr Foundation (support for overall trial), Dutch Heart Foundation (recruitment in The Netherlands) 

Coronary artery bypass grafting (CABG) is surgery used to treat people with coronary heart disease. It usually involves taking an artery that supplies blood to the inner chest and using it to bypass a narrowed area of coronary artery supplying the heart. Surgeons then use additional vessel ‘grafts’ (usually pieces of artery from the arm, or vein from the leg) as needed. There’s some evidence that - when multiple grafts are needed - it’s better if multiple artery grafts (MAG) are used, rather than a single arterial graft (SAG) and additional veins. This is because grafted veins are more likely to become blocked or diseased over time than arteries. But despite these potential benefits, currently in the UK MAG is only used for about 9% of men and 7% of women undergoing CABG. It’s a more technically difficult surgery to do – particularly in women, who tend to be physically smaller than men – and has also been linked to an increased risk of complications from the surgical wound. Previous randomised clinical trials (the gold standard way of testing a treatment) have not shown a clear difference in longer term outcomes between people who received MAG or SAG, but less than 20% of people who took part in previous trials were women. The team behind ROMA-Women want to address this knowledge gap by carrying out the first ever heart surgery trial to involve only women. They aim to enrol 2000 women undergoing CABG, who will be randomly assigned to receive either MAG or SAG during their surgery and followed up for up to 4 years (looking for any difference in the risk of dying, having a heart attack or stroke, needing a repeat surgery or hospitalisation between the two). If the results are positive, ROMA-Women could lead to a change in clinical guidelines, more women receiving MAG, and improved outcomes for women undergoing CABG. As CABG is the most commonly performed heart surgery in adults worldwide, the findings have the potential to improve the health of many millions of women.