Rapid Assessment of Potential Ischaemic Heart Disease With CTCA (RAPID-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.

This study aims to investigate the effect of early CTCA in patients with suspected or confirmed Acute Coronary Syndrome (ACS) presenting to the Emergency Department (ED) or Medical Assessment Unit (MAU), upon interventions, event rates and health care costs in a pragmatic clinical trial and economic evaluation up to 1 year after the trial intervention. The primary objective will be to investigate the effect of the intervention on all-cause death or subsequent type 1 or type 4b MI at one year, measured as time to first such event.

Study Overview

• Status: Unknown
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Radiation: CT Coronary Angiogram

Detailed Description

DESIGN: Open parallel group randomised controlled trial of early computed tomography coronary angiography (CTCA) in patients presenting with suspected/confirmed acute coronary syndrome (ACS) to Emergency Departments (ED) and Medical Assessment Units.

SETTING: 37 EDs, radiology, cardiology and acute medical services in tertiary/district general National Health Service (NHS) hospitals.

TARGET POPULATION: Inclusion Criteria: Patient ≥18 years with symptoms mandating investigation for suspected or confirmed ACS with at least one of: ECG abnormalities e.g. ST segment depression >0.5 mm; History of ischaemic heart disease (where the clinician assessing patient confirms history based on patient history or available records); 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). 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

HEALTH TECHNOLOGIES BEING ASSESSED: Early use of ≥64-slice CTCA as part of routine assessment compared to standard care.

MEASUREMENT OF COSTS/OUTCOMES: Primary end-point will be one-year all-cause death or subsequent type 1 or type 4b MI at one year, measured as time to first such event. Secondary endpoints: 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; Coronary

Heart Disease (CHD) death or subsequent non-fatal MI (type 1 or 4b);Subsequent Non-fatal MI (type 1 or 4b); Non-cardiovascular death; Invasive coronary angiography; Coronary revascularisation; Percutaneous coronary intervention; Coronary artery bypass graft; Proportion of patients prescribed ACS therapies during index hospitalisation; Proportion of patients discharged on preventative treatment or have alteration in dosage of preventative treatment during index hospitalisation; Length of stay for index hospitalisation; Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months after index hospitalisation; Chest pain symptoms up to 12 months; Patient satisfaction at 1 month; Clinician certainty of presenting diagnosis after CTCA; Quality of Life (measured by EQ- 5D-5L up to12 months). Adverse Events and Serious Adverse Events; Proportion of patients with alternative cardiovascular diagnoses identified on CTCA; Proportion of patients with non-cardiovascular diagnosis identified on CTCA; Radiation exposure from CTCA as trial intervention. Cost effectiveness:

Estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained.

SAMPLE SIZE: 1,749 patients.

• Study Type: Interventional
• Enrollment (Actual): 1749
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Jersey
  • St Helier, Jersey
    • Jersey General Hospital
• United Kingdom
  • Basildon, United Kingdom
    • Basildon and Thurrock University Hospitals NHS Foundation Trust
  • Belfast, United Kingdom
    • Ulster Hospital
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Bournemouth, United Kingdom
    • The Royal Bournemouth and Christchurch Hospital
  • Bradford, United Kingdom
    • Bradford Royal Infirmary
  • Dudley, United Kingdom
    • Russells Hall Hospital
  • Dundee, United Kingdom
    • Ninewells Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary Edinburgh
  • Glasgow, United Kingdom
    • Glasgow Royal Infirmary
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • Inverness, United Kingdom
    • Raigmore Hospital
  • Kirkcaldy, United Kingdom
    • Victoria Hospital
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • Lewisham, United Kingdom
    • University Hospital Lewisham
  • London, United Kingdom
    • Royal London Hospital
  • London, United Kingdom
    • St. Thomas' Hospital
  • London, United Kingdom
    • University Hospital North Tees
  • London, United Kingdom
    • Whipps Cross Hospital
  • Luton, United Kingdom
    • Luton & Dunstable Hospital
  • Melrose, United Kingdom
    • Borders General Hospital
  • Milton Keynes, United Kingdom
    • Milton Keynes University Hospital NHS Foundation Trust
  • Newcastle, United Kingdom
    • Royal Victoria Infirmary
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Portsmouth, United Kingdom
    • Queen Alexandra Hospital
  • Reading, United Kingdom
    • Royal Berkshire NHS foundation trust
  • Redhill, United Kingdom
    • East Surrey Hospital
  • Rotherham, United Kingdom
    • Rotherham Hospital
  • Sandwell, United Kingdom
    • Sandwell General Hospital
  • Sheffield, United Kingdom
    • Northern General Hospital
  • Southampton, United Kingdom
    • University Hospital Southampton Nhs Foundation Trust
  • Stoke, United Kingdom
    • University Hospitals of the Midlands
  • Torquay, United Kingdom
    • Torbay Hospital
  • Wolverhampton, United Kingdom
    • New Cross Hospital
  • Worcester, United Kingdom
    • Worcestershire Royal Hospital
  • Wrexham, United Kingdom
    • Wrexham Maelor Hospital
  • Wythenshawe, United Kingdom
    • University Hospital South Manchester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

Patient ≥18 years with symptoms mandating investigation for suspected or confirmed ACS with at least one of:

• ECG abnormalities e.g. ST segment depression >0.5 mm;
• History of ischaemic heart disease (where the clinician assessing patient confirms history based on patient history or available records);
• 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).

EXCLUSION CRITERIA

• 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.

• 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).
• 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.
• Previous recruitment to the trial;
• Known pregnancy or currently breast feeding;
• Inability to consent;
• Further investigation for ACS would not in the patient's interest, due to limited life expectancy, quality of life or functional status;
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CT Coronary Angiogram; CT Coronary Angiogram plus standard care	Radiation: CT Coronary Angiogram; Completion of a CT Coronary Angiogram
No Intervention: Standard Care; Standard care only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary end-point will be all-cause death or subsequent non-fatal type 1 or type 4b MI at one year, measured as 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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Heart Disease (CHD) death or subsequent non-fatal MI	Death or MI	1 year
Cardiovascular Disease (CVD) death or subsequent non-fatal MI	CVD Death	1 year
Subsequent Non-fatal MI	MI	1 year
Coronary Heart Disease death	CHD Death	1 year
Cardiovascular death	CVS Death	1 year
All-cause death	Death	1 year
Coronary Heart Disease (CHD) death or subsequent non-fatal MI (type 1 or 4b)	CHD and MI	1 year
Subsequent Non-fatal MI (type 1 or 4b)	Non Fatal MI	1 year
Non-cardiovascular death	Non CVS Death	1 year
Invasive coronary angiography	Angiography procedures	1 year
Coronary revascularisation	Revascularisation procedures	1 year
Percutaneous coronary intervention	PCI interventions	1 year
Coronary artery bypass graft	CABG procedures	1 year
Proportion of patients prescribed ACS therapies during index hospitalisation	ACS therapies	1 year
Proportion of patients discharged on preventative treatment or have alteration in dosage of preventative treatment during index hospitalisation	Preventative treatments	1 year
Length of Stay for Index Hospitalisation	Length of Stay	1 year
Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months after index hospitalisation	Hospital attendances for ACS	1 year
Chest pain symptoms up to 12 months	Patient symptoms measured by ROSE questionnaire	1 year
Quality of Life (measured by EQ-5D-5L up to 12 months)	Quality of life measured by EQ-5D-5L questionnaire	1 year
Patient satisfaction at 1 month	Participant questionnaire (11 questions) asking their viewpoint on the care they received during their baseline admission.	1 year
Clinician certainty of presenting diagnosis after CTCA	Clinician certainty	1 year
Proportion of patients with alternative cardiovascular diagnoses identified on CTCA	Safety assessment AE and SAEs	1 year
Proportion of patients with non-cardiovascular diagnosis identified on CTCA	Safety Assessment AEs and SAEs	1 year
Radiation exposure from CTCA as trial intervention	Safety Assessment AEs and SAEs	1 year
Cost effectiveness	Estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained.	1 year

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian

Publications and helpful links

General Publications

• Meah MN, Tzolos E, Wang KL, Bularga A, Dweck MR, Curzen N, Kardos A, Keating L, Storey RF, Mills NL, Slomka PJ, Dey D, Newby DE, Gray A, Williams MC, Roobottom C. Plaque Burden and 1-Year Outcomes in Acute Chest Pain: Results From the Multicenter RAPID-CTCA Trial. JACC Cardiovasc Imaging. 2022 Nov;15(11):1916-1925. doi: 10.1016/j.jcmg.2022.04.024. Epub 2022 Jun 15.
• Meah MN, Bularga A, Tzolos E, Chapman AR, Daghem M, Hung JD, Chiong J, Taggart C, Wereski R, Gray A, Dweck MR, Roobottom C, Curzen N, Kardos A, Felmeden D, Mills NL, Slomka PJ, Newby DE, Dey D, Williams MC. Distinguishing Type 1 from Type 2 Myocardial Infarction by Using CT Coronary Angiography. Radiol Cardiothorac Imaging. 2022 Oct 27;4(5):e220081. doi: 10.1148/ryct.220081. eCollection 2022 Oct.
• Gray AJ, Roobottom C, Smith JE, Goodacre S, Oatey K, O'Brien R, Storey RF, Curzen N, Keating L, Kardos A, Felmeden D, Lee RJ, Thokala P, Lewis SC, Newby DE. Early computed tomography coronary angiography in adults presenting with suspected acute coronary syndrome: the RAPID-CTCA RCT. Health Technol Assess. 2022 Aug;26(37):1-114. doi: 10.3310/IRWI5180.
• Gray AJ, Roobottom C, Smith JE, Goodacre S, Oatey K, O'Brien R, Storey RF, Curzen N, Keating L, Kardos A, Felmeden D, Lee RJ, Thokala P, Lewis SC, Newby DE; RAPID-CTCA Investigators. Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial. BMJ. 2021 Sep 29;374:n2106. doi: 10.1136/bmj.n2106. Erratum In: BMJ. 2022 Feb 21;376:o438.
• Gray AJ, Roobottom C, Smith JE, Goodacre S, Oatey K, O'Brien R, Storey RF, Na L, Lewis SC, Thokala P, Newby DE. The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) - a multicentre parallel-group randomised trial to compare early computerised tomography coronary angiography versus standard care in patients presenting with suspected or confirmed acute coronary syndrome: study protocol for a randomised controlled trial. Trials. 2016 Dec 7;17(1):579. doi: 10.1186/s13063-016-1717-2.

Helpful Links

• Protocol publication

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): June 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: October 6, 2014
• First Submitted That Met QC Criteria: November 3, 2014
• First Posted (Estimate): November 5, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2020
• Last Update Submitted That Met QC Criteria: August 27, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Emergency Medicine; Radiology; Cardiology; Acute Medicine
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: RAPID-CTCA-2014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No