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

• ClinicalTrials.gov Identifier: NCT02284191
• Recruitment Status: Unknown
• First Posted: November 5, 2014
• Last Update Posted: August 31, 2020
• Sponsor: University of Edinburgh
• Collaborator: NHS Lothian
• Information provided by (Responsible Party): University of Edinburgh

Tracking Information

• First Submitted Date: October 6, 2014
• First Posted Date: November 5, 2014
• Last Update Posted Date: August 31, 2020
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 9, 2020)

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. [ Time Frame: 1 year ]

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.

Original Primary Outcome Measures (submitted: November 3, 2014)

The primary end-point will be all-cause death or recurrent non-fatal type type 1 and 4b myocardial infarction. [ Time Frame: 1 year ]

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.

Current Secondary Outcome Measures (submitted: July 9, 2020)

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

Original Secondary Outcome Measures (submitted: November 3, 2014)

• Hospital length of stay [ Time Frame: 1 year ]
• Coronary care length of stay [ Time Frame: 1 year ]
• Proportion of patients receiving invasive coronary angiography during index hospitalisation [ Time Frame: 1 year ]
• Proportion of patients receiving coronary revascularisation during index hospitalisation [ Time Frame: 1 year ]
• Proportion of patients receiving subsequent unplanned coronary revascularisation after index hospitalisation within 12 months [ Time Frame: 1 year ]
• Proportion of patients in CTCA arm receiving invasive coronary angiography despite <50% stenosis on CTCA [ Time Frame: 1 year ]
• Proportion of patients prescribed ACS therapies and/or discharged on secondary prevention treatment during index hospitalisation [ Time Frame: 1 year ]
• Representation or rehospitalisation with suspected ACS/recurrent chest pain within 12 months [ Time Frame: 1 year ]
• Patient symptoms (up to 12 months) ROSE Questionnaire [ Time Frame: 1 year ]
  Patient symptoms measured by ROSE questionnaire
• Patient quality of life (up to 12 months) EQ-5D-5L questionnaire [ Time Frame: 1 year ]
  Quality of life measured by EQ-5D-5L questionnaire
• NHS resource utilisation [ Time Frame: 1 year ]
• Patient satisfaction with care questionnaire [ Time Frame: 1 year ]
  Participant questionnaire (11 questions) asking their viewpoint on the care they received during their baseline admission.
• Proportion of patients with allergy/anaphylaxis/acute kidney injury [ Time Frame: 1 year ]
  Safety assessment
• Proportion of patients with alternative diagnoses e.g. aortic dissection or incidental but potentially concerning e.g. malignancy or pulmonary nodules. [ Time Frame: 1 year ]
  Safety assessment
• Total radiation exposure in each arm. [ Time Frame: 1 year ]
  Safety assessment
• Cost effectiveness [ Time Frame: 1 year ]
  Estimated in terms of the lifetime incremental cost per quality-adjusted life year (QALY) gained.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Diagnostic
• Condition: Acute Coronary Syndrome

Intervention

Radiation: CT Coronary Angiogram

Completion of a CT Coronary Angiogram

Study Arms

• Active Comparator: CT Coronary Angiogram
  CT Coronary Angiogram plus standard care
  Intervention: Radiation: CT Coronary Angiogram
• No Intervention: Standard Care
  Standard care only

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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: July 9, 2020): 1749
• Original Estimated Enrollment (submitted: November 3, 2014): 2500
• Estimated Study Completion Date: December 2020
• Actual Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Jersey, United Kingdom

Administrative Information

• NCT Number: NCT02284191
• Other Study ID Numbers: RAPID-CTCA-2014
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Edinburgh
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Edinburgh
• Original Study Sponsor: Same as current
• Collaborators: NHS Lothian

Investigators

• Principal Investigator: Alasdair J Gray; NHS Lothian

• PRS Account: University of Edinburgh
• Verification Date: August 2020