Title: Controlled trial of High-risk coronary Intervention with Percutaneous left ventricular unloading (CHIP-BCIS3)
Funder: Department of Health and Social Care

Abstract: Over 100,000 coronary stent procedures, where small balloons are used to stretch open a narrowed blood vessel supplying the heart, are performed every year in the UK to treat people who have conditions such as angina or have suffered a heart attack._x000D_ _x000D_ For most patients the risk of complications is low, but for some there is a higher risk of their heart failing during the procedure. Heart failure is a serious complication which can need treatment with a life support machine and lead to major damage to the heart muscle or even death. These risks are greatest in patients with severely diseased heart arteries and those who already have weakened heart muscle._x000D_ _x000D_ A new technology may be able to help with this problem. It consists of a small heart pump which is placed in the heart’s main pumping chamber (the left ventricle). The pump is inserted into the heart through a blood vessel in the leg and supports the heart muscle. It is removed at the end of the procedure or when the heart can pump safely on its own. Whilst this heart pump is promising, it comes with some risks of its own. These include bleeding and damage to the arteries in the legs. It is also expensive, costing £8,000 per operation. The technology was recently covered by the BBC news, available online at https://www.bbc.co.uk/news/av/uk-england-bristol-48554543/smallest-heart-pump-helps-patients-in-bristol_x000D_ _x000D_ The National Institute for Health and Clinical Excellence (NICE) published a report on heart pumps in November 2018. They concluded that there was not enough information available, and that research is urgently needed to decide whether heart pumps are beneficial and cost-effective. The current NICE information for patients can be found at https://www.nice.org.uk/guidance/ipg633/informationforpub. This research study is designed to answer these questions._x000D_ _x000D_ This research will involve 250 people undergoing coronary stent operations. We will select patients who are at high risk of complications during the procedure. Half of these will have the heart pump inserted and the other half will have the normal stenting procedure – which patient receives which treatment will be decided at random by a computer. By monitoring these patients’ health during their initial recovery and over the following year, we will be able to tell whether the heart pump benefits patients._x000D_ _x000D_ One of the reasons why we don't already know whether the heart pump will benefit patients is that researchers would usually need to compare large numbers of patients to be sure of the result. Our statistics experts have developed a new way of analysing the information so that almost every patient’s information will be used to determine which treatment is best. This means we need a smaller number of people to be included, allowing us to understand the outcome sooner and reduce the burden on patients._x000D_ _x000D_ A patient group has helped to design the study, and the committee in charge of the project will include two representatives of patients and the public. Having support from these groups and representatives in managing the trial will help us to ensure the research respects the involvement of patients and answers questions which are truly important to those who use the NHS._x000D_ _x000D_ On completing this study, the results will be published in medical journals and at conferences. The results will be used by NICE in writing future information sheets for patients who are being offered this treatment, as well as medical guidelines.

Lay abstract: Background_x000D_ _x000D_ Percutaneous coronary intervention (PCI) is the most common method used to treat coronary heart disease. The benefits need to be balanced against the risk of major complications (including death, stroke, periprocedural myocardial infarction and acute heart failure), which are particularly likely to occur in those patients with pre-existing heart failure, need complex interventions and have extensive coronary disease which jeopardises a large proportion of the myocardium._x000D_ _x000D_ Percutaneous left ventricular (LV) unloading devices offer the potential to reduce complications for patients who undergo high-risk PCI. NICE recently approved the technology, despite an acknowledged lack of evidence for efficacy and safety concerns; use has been increasing both in the UK and internationally. The only randomised evidence for LV unloading to date comes from an industry-sponsored trial which used a comparator arm which does not represent the current standard of care and was stopped prematurely due to the predicted inability to demonstrate efficacy. The investigators did not report key safety data or medium-to-long term outcomes._x000D_ _x000D_ Aim_x000D_ _x000D_ To establish whether, in patients undergoing high-risk percutaneous coronary intervention, a strategy of percutaneous LV unloading is superior to standard care in terms of patient outcomes, quality of life and cost-effectiveness._x000D_ _x000D_ Methods_x000D_ _x000D_ We propose a pragmatic, prospective randomised controlled trial across a network of 10-14 hospitals in the UK. Participants undergoing high-risk PCI (defined by the presence of extensive coronary disease, severely impaired left ventricular function and a need for complex coronary intervention) will be randomly allocated in 1:1 ratio to undergo the intervention (high-risk PCI with LV unloading) or standard care (high-risk PCI without mechanical circulatory support). _x000D_ _x000D_ The primary endpoint will be a combined hierarchical endpoint of death, stroke, spontaneous myocardial infarction, cardiovascular hospitalisation (including extension of hospitalisation for complications of the initial PCI procedure) and periprocedural myocardial infarction, over the entire duration of follow-up. _x000D_ _x000D_ The primary analysis will use the Win Ratio method which will account for the importance of each component event as well as repeated events within patients, as opposed to a traditional time-to-first-event analysis. This method is expected to increase power in situations where crossovers to the alternative treatment is low following the first event which will be the case in this trial. Sample sizes for Win Ratios are not well-established so using a more conventional time-to-first-event approach to illustrate the minimum power expected a sample size of 250 participants (125 in each arm) will provide well in excess of 80% power to detect a hazard ratio of 0.62 using events over all follow-up. This represents a risk ratio of 0.70 at 12 months based on a 50% event rate in the standard arm at 12 months. A risk reduction of this magnitude is required given the significant clinical and resource implications of using the devices, and therefore the necessary clinical gain to achieve cost effectiveness. However, with the Win Ratio for repeated events as the primary analysis, power is expected to be increased allowing for smaller differences to be detected or for lower event rates than anticipated. Key secondary outcomes include health-related quality of life and economic analyses. _x000D_ _x000D_ The planned project duration is 72 months.

Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR