Rapid Assessment of Potential Ischaemic heart Disease with Computed Tomography Coronary Angiography (CTCA)

ISRCTN	ISRCTN19102565
DOI	https://doi.org/10.1186/ISRCTN19102565
ClinicalTrials.gov (NCT)	NCT02284191
Protocol serial number	HTA 13/04/108
Sponsor	The University of Edinburgh (UK)
Funder	Health Technology Assessment Programme (Ref: 13/04/108)

Submission date: 03/10/2014
Registration date: 07/10/2014
Last edited: 06/09/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Recent advances in imaging technology have given us a non-invasive technique called computed tomography coronary angiography (CTCA). However, this technology has not been tested with patients presenting with suspected or confirmed acute coronary syndrome (e.g. heart attack) to the Emergency Department (ED) in the UK. CTCA is capable of giving a better treatment of such patients with suspected or confirmed acute coronary syndrome. This study aims to find out the effect of early CTCA for Emergency Department patients with suspected or confirmed ACS, compared to current standard practice. We also would like to see if this would be cost-effective to the practice.

Who can participate?
All patients aged 18 or over with suspected or confirmed ACS.

What does the study involve?
Eligible participants will be approached in the ED, Medical Assessment Unit (MAU) or Cardiology Unit and asked if they are willing to take part. They will be randomly allocated to CTCA in addition to standard care or standard care alone. During their admission and after 1, 6 and 12 months all participants will be asked to complete questionnaires about their symptoms, quality of life, satisfaction with their care and how often they have had to use healthcare services. Participants will be in the study for one year.

What are the possible benefits and risks of participating?
It is possible that the results of the scan will help your doctor decide whether or not there is any narrowing or blockage of the blood vessels around your heart. It may also show additional unknown problems in the heart and chest that may not have been detected otherwise. The scan can also reveal other potential causes for your chest pain. We hope that the research will also benefit many more people by helping us decide the best way to treat patients with your condition in the future. A CT Coronary Angiogram is a routine medical procedure. The scan itself is associated with very few side effects. The most important potential side effect, as with an x-ray or CT scan, is the use of radiation. The amount of radiation used during the scan varies but is around two to three times the amount you would normally receive in a year from background natural sources such as cosmic rays. The average excess risk of developing cancer due to a CT scan is 4 in 10,000 compared to a lifetime risk of 1 in 3. There is a very low risk of developing a reaction to the contrast agent. This usually involves an itchy rash that settles down by itself. Occasionally people require additional medications for this. If you are known to have an allergy to the contrast agent you will not be eligible to take part in the study. There is a possibility that the scan could reveal an incidental health problem that you or your doctor is unaware of. If this were to happen we would discuss this with your doctor and arrange appropriate further tests and treatments as necessary.

Where is the study run from?
This study is being co-ordinated by an experienced research team at the University of Edinburgh in collaboration with NHS Lothian. They work closely with doctors and nurses in local research teams in various hospitals throughout the UK.

When is the study starting and how long is it expected to run for?
January 2015 to June 2020 (updated 15/07/2020, previously: December 2018)

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr Alasdair Gray
alasdair.gray@nhslothian.scot.nhs.uk

Contact information

Prof Alasdair Gray
Scientific

EMeRGE Office
Department of Emergency Medicine
Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Phone	+44 (0)131 242 1340
Email	alasdair.gray@nhslothian.scot.nhs.uk

Study information

Primary study design	Interventional
Study design	Open prospective parallel-group randomised controlled trial
Secondary study design	Randomised parallel trial
Study type	Participant information sheet
Scientific title	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
Study acronym	RAPID-CTCA
Study objectives	This study aims to investigate the effect of early CTCA for ED patients with suspected or confirmed ACS, compared to current standard practice, upon interventions, event rates and health care costs in a pragmatic clinical trial and economic evaluation up to 1 year after the trial. More details can be found at http://www.nets.nihr.ac.uk/projects/hta/1304108 Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0007/136996/PRO-13-04-108.pdf
Ethics approval(s)	South East Scotland Ethics Committee, 15/12/2014, ref: 14/SS/1096
Health condition(s) or problem(s) studied	Emergency/Acute Medicine, Radiology, Cardiology
Intervention	Consented patients will be randomised on a 1:1 basis to CTCA in addition to standard care or standard care alone. All participants will be asked to complete questionnaires at baseline and 1, 6 and 12 months to record QoL, symptoms, patient satisfaction and health services usage.
Intervention type	Other
Primary outcome measure(s)	Current primary outcome measure as of 15/07/2020: All-cause death or subsequent non-fatal type 1 or type 4b MI at one year, measured as time to first such event. MI will be defined according to the most recent Universal Definition [Thygesen K, 2012] and will be adjudicated by two independent cardiologists blinded to the intervention. Previous primary outcome measures as of 19/01/2016: All-cause death or recurrent non-fatal type 1 or type 4b myocardial infarction at one year and time to first such event. Myocardial infarction will be defined according to the most recent Universal Definition [Thygesen K, 2012] and will be adjudicated by two independent cardiologists blinded to the intervention. Previous primary outcome measures: All-cause death or recurrent non-fatal type 1 or type 4b myocardial infarction. Myocardial infarction will be defined according to the most recent Universal Definition and will be adjudicated by two independent cardiologists blinded to the intervention.
Key secondary outcome measure(s)	Current secondary outcome measures as of 15/07/2020: Key Secondary Endpoints 1. Coronary Heart Disease (CHD) death or subsequent non-fatal MI 2. Cardiovascular Disease (CVD) death or subsequent non-fatal MI 3. Subsequent Non-fatal MI 4. Coronary Heart Disease death 5. Cardiovascular death 6. All-cause death Other Endpoints 8. Coronary Heart Disease (CHD) death or subsequent non-fatal MI (type 1 or 4b) 9. Subsequent Non-fatal MI (type 1 or 4b) 10. Non-cardiovascular death 11. Invasive coronary angiography 12. Coronary revascularisation 13. Percutaneous coronary intervention 14. Coronary artery bypass graft 15. Proportion of patients prescribed ACS therapies during index hospitalisation 16. Proportion of patients discharged on preventative treatment or have alteration in dosage of preventative treatment during index hospitalisation 17. Length of stay for index hospitalisation 18. Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months after index hospitalisation; 19. Chest pain symptoms up to 12 months 20. Patient satisfaction at 1 month 21. Clinician certainty of presenting diagnosis after CTCA 22. Quality of Life (measured by EQ-5D-5L up to12 months) 23. Adverse Events and Serious Adverse Events: 23.1. Proportion of patients with alternative cardiovascular diagnoses identified on CTCA 23.2. Proportion of patients with non-cardiovascular diagnosis identified on CTCA 23.3. Radiation exposure from CTCA as trial intervention 24. Cost effectiveness: estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained Previous secondary outcome measures as of 19/01/2016: 1. Hospital length of stay, coronary care length of stay 2. Proportion of patients receiving invasive coronary angiography during index hospitalisation 3. Proportion of patients receiving coronary revascularisation during index hospitalisation 4. Proportion of patients receiving subsequent unplanned coronary revascularisation after index hospitalisation within 12 months 5. Proportion of patients in CTCA arm receiving invasive coronary angiography despite <50% stenosis on CTCA 6. Proportion of patients assigned to CTCA with normal or mild non-obstructive disease 7. Proportion of patients prescribed ACS therapies and/or discharged on secondary prevention treatment or have alteration in dosage of secondary preventive treatment during index hospitalisation 8. Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months 9. Patient symptoms and quality of life up to 12 months 10. NHS resource utilisation 11. Patient satisfaction 12. Clinician certainty of presenting diagnosis after CTCA. Safety: 1. Proportion of patients with allergy/anaphylaxis/acute kidney injury; 2. Proportion of patients with alternative diagnoses that relates to presentation on CTCA e.g. aortic dissection or pulmonary embolus 3. Proportion of patients with incidental finding but potentially concerning on CTCA e.g. malignancy or pulmonary nodules 4. Total average radiation exposure from CTCA in the intervention arm during index hospitalisation. Cost effectiveness: Estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained. Previous secondary outcome measures: 1. Hospital length of stay, coronary care length of stay 2. Proportion of patients receiving invasive coronary angiography during index hospitalisation 3. Proportion of patients receiving coronary revascularisation during index hospitalisation 4. Proportion of patients receiving subsequent unplanned coronary revascularisation after index hospitalisation within 12 months 5. Proportion of patients in CTCA arm receiving invasive coronary angiography despite <50% stenosis on CTCA 6. Proportion of patients assigned to CTCA with normal or non-diagnostic imaging 7. Proportion of patients prescribed ACS therapies and/or discharged on secondary prevention treatment during index hospitalisation 8. Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months 9. Patient symptoms and quality of life up to 12 months 10. NHS resource utilisation 11. Patient satisfaction Safety: 1. Proportion of patients with allergy/anaphylaxis/acute kidney injury 2. Proportion of patients with alternative diagnoses e.g. aortic dissection or incidental but potentially concerning e.g. malignancy or pulmonary nodules 3. Total radiation exposure in each arm Cost effectiveness: Estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained
Completion date	30/06/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	1735
Total final enrolment	1748
Key inclusion criteria	Current inclusion criteria as of 19/01/2016: Patients ≥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’ or myocardial infarction (NB troponin assays will vary from site to site; local laboratory reference standards will be used). Previous inclusion criteria: Patients aged 18 years or older 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 3. Troponin elevation above the 99th centile of the normal reference range (NB troponin assays will vary from site to site; local laboratory reference standards will be used).
Key exclusion criteria	Current exclusion criteria as of 19/01/2016: 1. Signs, symptoms, or investigations supporting high-risk ACS: 1.1. ST elevation MI 1.2. ACS with signs or symptoms of acute heart failure or circulatory shock 1.3. Crescendo episodes of typical anginal pain 1.4. Marked or dynamic ECG changes e.g. ST depression of >3 mm 1.5. Clinical team have scheduled early invasive coronary angiography on day of trial eligibility assessment 2. Patient inability to undergo CT: 2.1. Severe renal failure (serum creatinine >250 µmol/L or estimated glomerular filtration rate <30 mL/min) 2.2. Contrast allergy 2.3. Beta blocker intolerance (if no alternative heart rate limiting agent available/suitable) or allergy 2.4. Inability to breath hold 2.5. 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 breastfeeding 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 Previous 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 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; inability to hold breath; atrial fibrillation (mean heart rate greater than 75 beats per minute) 3. Invasive coronary angiography or CTCA within last 2 years if the previous investigation revealed CAD, 5 years if previous investigation normal 4. Previous recruitment to the trial 5. Known pregnancy 6. Inability to consent 7. Further investigation for ACS would not in the patients interest, due to limited life expectancy, quality of life or functional status 8. Prisoners
Date of first enrolment	11/03/2015
Date of final enrolment	30/06/2019

Locations

Countries of recruitment

United Kingdom
England
Northern Ireland
Scotland
Wales
Jersey

Study participating centres

Royal Infirmary of Edinburgh

Edinburgh
EH16 4SA
United Kingdom

Sheffield Northern General Hospital

Sheffield
S5 7AU
United Kingdom

Plymouth Derriford Hospital

Plymouth
PL6 8DH
United Kingdom

Torbay Hospital

Torquay
TQ2 7AA
United Kingdom

Victoria Hospital

Kirkcaldy
KY2 5AH
United Kingdom

Russells Hall Hospital

Dudley
DY1 2HQ
United Kingdom

Royal Berkshire NHS Foundation Trust

Reading
RG1 5AN
United Kingdom

Bradford Teaching Hospitals NHS Foundation Trust

Bradford
BD9 6RJ
United Kingdom

Royal Bournemouth Hospital

Bournemouth
BH7 7DW
United Kingdom

Jersey General Hospital

Saint Helier
JE1 3QS
Jersey

Borders General

Melrose
TD6 9BS
United Kingdom

Royal Victoria Infirmary

Newcastle
NE7 7DN
United Kingdom

Lewisham University Hospital

London
SE13 6LH
United Kingdom

Glasgow Royal Infirmary

Glasgow
G4 0SF
United Kingdom

Milton Keynes Hospital NHS Foundation Trust

Milton Keynes
MK6 5LD
United Kingdom

University Hospitals of the North Midlands (UHNM)

Stoke-on-Trent
ST4 6QG
United Kingdom

Sandwell General Hospital

West Bromwich
B71 4HJ
United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London
SE1 7EH
United Kingdom

Rotherham General Hospital

Rotherham
S60 2UD
United Kingdom

Leeds General Infirmary

Leeds
LS1 3EX
United Kingdom

Queen Elizabeth Hospital

Birmingham
B15 2TH
United Kingdom

Surrey & Sussex Hospitals (East Surrey Hospital)

Redhill
RH1 5RH
United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton
SO16 6YD
United Kingdom

Manchester University NHS Foundation Trust (MFT)

Manchester
M23 9LT
United Kingdom

Luton and Dunstable University Hospital

Luton
LU4 0DZ
United Kingdom

Barts Health NHS Trust Royal London Hospital

London
EC1A 7BE
United Kingdom

Whipps Cross University Hospital

London
E11 1NR
United Kingdom

Worcestershire Acute Hospitals NHS Trust

Worcester
WR5 1DD
United Kingdom

Ulster Hospital

Belfast
BT16 1RH
United Kingdom

University Hospital North Tees

Stockton-on-Tees
TS19 8PE
United Kingdom

Ninewells Hospital, NHS Tayside

Dundee
DD1 9SY
United Kingdom

Queen Alexandra Hospital

Portsmouth
PO6 3LY
United Kingdom

Betsi Cadwaladr University Health Board (Wrexham Maelor Hospital)

Wrexham
LL13 7TD
United Kingdom

Basildon and Thurrock University Hospitals NHS Foundation Trust

Basildon
SS16 5NL
United Kingdom

The Royal Wolverhampton NHS Trust

Wolverhampton
WV10 0QP
United Kingdom

Raigmore Hospital

Inverness
IV2 3UJ
United Kingdom

Queen Elizabeth University Hospital

Glasgow
G51 4TF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	29/09/2021	04/10/2021	Yes	No
Results article	HTA report	01/08/2022	06/09/2022	Yes	No
Protocol article	protocol	07/12/2016		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

06/09/2022: Publication reference added.
04/10/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
15/01/2021: Internal review.
15/07/2020: The following changes were made to the trial record:
1. The primary outcome measure was changed.
2. The secondary outcome measures were changed.
3. The plain English summary was updated to reflect earlier changes.
14/01/2019: The following changes were made:
1. The recruitment end date was changed from 31/12/2018 to 30/06/2019.
2. The overall trial end date was changed from 01/06/2020 to 30/06/2020.
3. The target number of participants was changed from 2500 to 1735.
4. The intention to publish date was changed from 30/06/2020 to 30/06/2021.
5. All trial participating centres, apart from Edinburgh Royal Infirmary, have been added.
15/09/2017: Individual patient level data sharing statement has been added. Publication and dissemination plans have been added. The intention to publish date has been updated from 01/07/2019 to 30/06/2020. Overall trial dates have been updated from 01/06/2014-31/12/2018 to 01/01/2015-01/06/2020. Recruitment dates have been updated from 01/06/2014-01/06/2017 to 11/03/2015-31/12/2018.
08/09/2017: Internal review.
08/12/2016: Publication reference added.
30/03/2016: Ethics approval information added.