Title: The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) The role of early CT Coronary Angiography in the evaluation, intervention and outcome of patients presenting to the Emergency Department with suspected or confirmed Acute Coronary Syndrome
Funder: Chief Scientist Office, Scotland

Abstract: DESIGN: Open parallel group randomised controlled trial of early computed tomography coronary angiography (CTCA) in Emergency Department (ED) and Medical Assessment unit patients presenting with suspected/confirmed acute coronary syndrome (ACS). SETTING: ~35 EDs, radiology, cardiology and acute medical services in tertiary/district general NHS hospitals. TARGET POPULATION: Inclusion criteria: Patients greater than or equal to 18 years with symptoms mandating investigation for suspected or confirmed ACS with at least one of: 1. ECG abnormalities e.g. ST segment depression >0.5 mm; 2. History of ischaemic heart disease (where the clinician assessing patient confirms history based on patient history or available records); 3. Troponin elevation above the 99th centile of the normal reference range or increase in high sensitivity troponin meeting European Society of Cardiology criteria for ‘rule-in’ of myocardial infarction. Exclusion criteria: 1. Signs, symptoms, or investigations supporting high-risk ACS: ST elevation MI; ACS with signs or symptoms of acute heart failure or circulatory shock; Crescendo episodes of typical anginal pain; Marked or dynamic ECG changes e.g. ST depression of >3 mm; Clinical team have scheduled early invasive coronary angiography on day of trial eligibility assessment. 2. Patient inability to undergo CT: Severe renal failure (serum creatinine >250 µmol/L or estimated glomerular filtration rate <30 mL/min); Contrast allergy; Beta blocker intolerance (if no alternative heart rate limiting agent available/suitable) or allergy; Inability to breath hold; Atrial fibrillation (where mean heart rate is anticipated to be greater than 75 beats per minute after beta blockade). 3. Patient has had invasive coronary angiography or CTCA within last 2 years and the previous investigation revealed obstructive coronary artery disease, or patient had either investigation within the last 5 years and the result was normal. 4. Previous recruitment to the trial; 5. Known pregnancy or currently breast feeding; 6. Inability to consent; 7. Further investigation for ACS would not in the patient’s interest, due to limited life expectancy, quality of life or functional status; 8. Prisoners SAMPLE SIZE: 1725 participants. PROJECT TIMETABLE: Trial set up: May 2014-Oct 2014 Site Set up: Oct 2014-Feb 2017 Recruitment: Mar 2015-Jun 2019 12-Month Follow up: Mar 2016-Jun 2020 Analysis and reporting: Jul 2020-Sep 2020 Trial Closure: Sep 2020

Lay abstract: Coronary artery disease (CAD) occurs when narrowing develops in the blood vessels supplying the heart. If the blood vessels become obstructed the patient may develop an acute coronary syndrome (ACS) and be at risk of a heart attack, heart failure and death. Around 700,000 people attend hospital emergency departments (ED) each year with chest pain mainly for assessment for suspected ACS. Standard assessment involves using an electrocardiogram and troponin blood test. If both tests are negative then the patient is at low risk of a bad outcome and can often be discharged home. If either test is positive, the patient is at intermediate or high risk and requires hospital admission. While in hospital, patients may require invasive coronary angiography. This test accurately identifies coronary artery obstruction that can be then be treated, but involves passing a catheter into the heart and therefore carries significant risks. High risk patients are mostly investigated with invasive coronary angiography whilst in hospital because there is a substantial chance of finding a blocked artery that can be unblocked using the catheter and kept open using a stent. Intermediate risk patients are variably investigated with invasive coronary angiography because the risks may not justify the potential benefits. However, intermediate risk patients have a 20% risk of developing a serious heart problem over the following months. This could be reduced if their heart disease was more accurately investigated. Also, troponin testing is becoming more sensitive increasing the diagnosis of ACS but small rises may not reflect CAD or a blocked heart artery. If this results in more invasive coronary angiograms, this may increase patient risk and NHS costs without significant benefit. CT coronary angiography (CTCA) involves using a CT scan to identify coronary artery obstruction. It is slightly less accurate at identifying obstruction than invasive coronary angiography but has fewer risks. It could therefore be used to improve the investigation of intermediate risk patients. It could be used to identify patients with significant obstruction who require invasive coronary angiography, allowing treatment of the obstruction and reducing the risk of serious heart problems. It could also identify patients without significant obstruction who could be discharged home, thus avoiding unnecessary tests. However, although the ability of CTCA to detect obstruction is well known, it is unclear whether using CTCA leads to more appropriate use of coronary angiography, a reduced risk of serious heart problems and improved patient outcomes. We plan to undertake a trial of CTCA in patients admitted to hospital with suspected or confirmed ACS except high risk patients needing immediate coronary angiography. Eligible patients will be given information about the trial and asked to sign a consent form. Patients will be allocated to either receive CTCA as part of their assessment or receive standard assessment without this test. We will then follow patients for one year to determine the rate of adverse outcomes (such as heart attack or death), quality of life, patient satisfaction, the use of diagnostic tests or treatments, and health care costs. The trial will be undertaken by an experienced team of UK researchers involved in previous successful trials in patients with chest pain. The team includes experts in emergency medicine, cardiology, radiology, acute medicine, statistics and economics

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR