Clinical trial NCT02284191: Rapid Assessment of Potential Ischaemic Heart Disease With CTCA
Official 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
Keywords: Radiology
Acute Medicine
Emergency Medicine
Cardiology
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
First posted: 2014-11-05
Enrollment: 1749
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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 (1,748 available for analysis).

Eligibility criteria: 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

Primary outcomes:
measure: All-cause Death or Subsequent Non-fatal Type 1 or Type 4b MI at One Year Measured as Time to First Such Event.
timeFrame: 1 year (post randomisation)
Secondary outcomes:
measure: Coronary Heart Disease Death or Subsequent Non-fatal MI
timeFrame: 1 year (post randomisation)
measure: Cardiovascular Disease Death or Subsequent Non-fatal MI
timeFrame: 1 year (post randomisation)
measure: Subsequent Non-fatal MI
timeFrame: 1 year (post randomisation)
measure: Coronary Heart Disease Death
timeFrame: 1 year (post randomisation)
measure: Cardiovascular Death
timeFrame: 1 year (post-randomisation)
measure: All-cause Death
timeFrame: 1 year (post-randomisation)
measure: Coronary Heart Disease (CHD) Death or Subsequent Non-fatal MI (Type 1 or 4b)
timeFrame: 1 year (post randomisation)
measure: Subsequent Non-fatal MI (Type 1 or 4b)
timeFrame: 1 year (post-randomisation)
measure: Non-cardiovascular Death
timeFrame: 1 year (post-randomisation)
measure: Invasive Coronary Angiography
timeFrame: 1 year (post randomisation)
measure: Coronary Revascularisation
timeFrame: 1 year (post randomisation)
measure: Percutaneous Coronary Intervention
timeFrame: 1 year (post randomisation)
measure: Coronary Artery Bypass Graft
timeFrame: 1 year (post randomisation)
measure: Number of Patients Prescribed ACS Therapies During Index Hospitalisation
timeFrame: 1 year (post randomisation)
measure: Discharged on Preventative Treatment or Alteration in Dosage of Preventative Treatment During Index Hospitalisation
timeFrame: 1 year (post randomisation)
measure: Length of Stay for Index Hospitalisation
timeFrame: A maximum follow up of one-year post-randomisation.
measure: Representation or Rehospitalisation With Suspected ACS/ Recurrent Chest Pain After Index Hospitalisation
timeFrame: 1 year (post randomisation)
measure: Radiation Exposure From CTCA as Trial Intervention
timeFrame: 1 year (post randomisation)
Other outcomes:
Locations:
city: St Helier
country: Jersey
facility: Jersey General Hospital
city: Basildon
country: United Kingdom
facility: Basildon and Thurrock University Hospitals NHS Foundation Trust
city: Belfast
country: United Kingdom
facility: Ulster Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth and Christchurch Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary Edinburgh
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
city: Kirkcaldy
country: United Kingdom
facility: Victoria Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Lewisham
country: United Kingdom
facility: University Hospital Lewisham
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: London
country: United Kingdom
facility: University Hospital North Tees
city: London
country: United Kingdom
facility: Whipps Cross Hospital
city: Luton
country: United Kingdom
facility: Luton & Dunstable Hospital
city: Melrose
country: United Kingdom
facility: Borders General Hospital
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes University Hospital NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
city: Redhill
country: United Kingdom
facility: East Surrey Hospital
city: Rotherham
country: United Kingdom
facility: Rotherham Hospital
city: Sandwell
country: United Kingdom
facility: Sandwell General Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: Stoke
country: United Kingdom
facility: University Hospitals of the Midlands
city: Torquay
country: United Kingdom
facility: Torbay Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
city: Worcester
country: United Kingdom
facility: Worcestershire Royal Hospital
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
city: Wythenshawe
country: United Kingdom
facility: University Hospital South Manchester
Study officials:
affiliation: NHS Lothian
name: Alasdair J Gray
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24. No abstract available.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.