Coronary Computed Tomographic Angiography Combined With CT-FFR in Intermediate-Risk Chest Pain Patients.

Official title

A Prospective, Multicenter, Randomized Controlled Trial on the Impact of Coronary CTA Combined With CT-FFR on Diagnosis and Treatment Decisions and Clinical Outcomes in Emergency Patients With Intermediate Risk Chest Pain

Overview

This study aims to investigate the guiding value of coronary CTA combined with CT-FFR in diagnostic and treatment decision-making for emergency chest pain patients at moderate risk, as well as its impact on clinical outcomes. Through a prospective multicenter randomized controlled trial, this research compares the preventive effects of early application of this technology versus standard care on major adverse cardiovascular and cerebrovascular events (MACCE), with the goal of optimizing the diagnostic and treatment processes for emergency chest pain patients.

Detailed description

This study involves intermediate-risk emergency department patients presenting with chest pain or symptoms suggestive of acute coronary syndrome (ACS) but without acute myocardial infarction (AMI), defined by a HEART score greater than 3. After providing written informed consent, these patients are randomized to one of two strategies: an initial approach incorporating early coronary computed tomographic angiography (CCTA) or a standard care pathway without early CCTA. Patients in the CCTA group receive standard care as determined by their treating physician and undergo CCTA as soon as possible, typically within 24 hours and at most within 21 days. The results of the CCTA, including coronary artery stenosis severity and CT-derived fractional flow reserve (CT-FFR) values, are provided to the physician to inform further management, which may include invasive coronary angiography, medical therapy, or lifestyle interventions.

In contrast, patients randomized to the standard care group without early CCTA proceed with physician-directed evaluations that may include non-invasive functional tests such as exercise electrocardiography, stress echocardiography, or nuclear imaging according to local clinical practices, though CCTA is not part of their initial workup. Both groups receive optimal preventive care in line with current guidelines, and treating physicians are encouraged to initiate secondary prevention measures like antiplatelet therapy or statin use if any diagnostic tests reveal signs of coronary artery disease (CAD).

The primary endpoint of the study is a composite of death, readmission due to myocardial infarction, or hospitalization for unstable angina requiring revascularization. The trial aims to determine whether an early CCTA strategy improves diagnostic and treatment decision-making for intermediate-risk chest pain patients, ultimately influencing clinical outcomes compared to standard care. The study incorporates a prospective, multicenter design to ensure broad applicability and rigor, with careful attention to patient safety and adherence to ethical standards throughout the enrollment and follow-up processes.

Interventions

• Diagnostic test Coronary computed tomographic angiography with CT - derived fractional flow reserve
  A non-invasive coronary computed tomography angiography (CCTA) protocol that visualizes coronary anatomy to evaluate the presence, location, and severity of atherosclerotic stenosis, coupled with CT-derived fractional flow reserve (CT-FFR) analysis-a computational fluid dynamics method applied to CCTA datasets-to assess the hemodynamic significance of identified stenoses and identify lesions likely to induce myocardial ischemia.

Primary outcome measures

• Incidence of Major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and unstable angina pectoris [Time frame: The enrollment phase will last for 2 years, and follow-up for all participants will continue until 12 months after the last participant is enrolled.]

Secondary outcome measures (9)

• Incidence of Recurrent Emergency Department Visit for Chest Pain [Time frame: The enrollment phase will last for 2 years, and follow-up for all participants will continue until 12 months after the last participant is enrolled]
• Hospitalization Rate due to Chest Pain or Stroke [Time frame: 1 month; the enrollment phase will last for 2 years, and follow-up for all participants will continue until 12 months after the last participant is enrolled]
• Incidence of All-cause mortality [Time frame: The enrollment phase will last for 2 years, and follow-up for all participants will continue until 12 months after the last participant is enrolled.]
• Proportion of Patients Undergoing Invasive Coronary Angiography [Time frame: The enrollment phase will last for 2 years, and follow-up for all participants will continue until 12 months after the last participant is enrolled.]
• Proportion of Patients with Non-Obstructive CAD at Invasive Coronary Angiography [Time frame: The enrollment phase will last for 2 years, and follow-up for all participants will continue until 12 months after the last participant is enrolled.]
• Effect of an Early CCTA with CT-FFR Diagnostic Strategy on Preventive Medication Utilization (antiplatelet agents, lipid-lowering therapies) in Intermediate-Risk Emergency Department Chest Pain Patients [Time frame: 1 Year, 2 Year, 3 Year, 4 Year, and 5 Year.]
• Health economic evaluation endpoints [Time frame: 1 Year and 5 Year]
• Quality of Life Assessed by the Seattle Angina Questionnaire (SAQ) [Time frame: 1 Year and 5 Year]
• Quality of Life Assessed by the EQ-5D Index Scores [Time frame: 1 Year and 5 Year]

Eligibility criteria

Inclusion criteria

• Age≥18 years；
• Within 24 hours of presenting to the emergency department (ED) with chest pain or other symptoms suggestive of coronary artery disease (CAD)；
• HEART-score >3 (according to http://www.heartscore.nl/)；
• Signed written informed consent.

Exclusion criteria

• Inability to obtain informed consent；
• Acute Coronary Syndromes (ACS) requiring urgent revascularization；
• Known Obstructive Coronary Artery Disease (CAD) or previous PCI or CABG;
• Concomitant severe congestive heart failure (New York Heart Association \[NYHA\] class III-IV or left ventricular ejection fraction \[LVEF\] < 30%) or acute pulmonary edema;
• Severe hepatic insufficiency (Child-Pugh score ≥ C, or aspartate aminotransferase \[AST\] > 5× upper limit of normal); severe renal insufficiency (estimated glomerular filtration rate \[eGFR\] ≤ 30 mL/min/1.73 m²) or patients receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis;
• History of prior coronary artery bypass grafting (CABG);
• Severe allergy to iodinated contrast agents;
• Inability to obtain high-quality imaging;
• Pregnant or lactating females;
• Concomitant diseases or limited life expectancy, quality of life, or functional status precluding further CAD evaluation;
• Any other factors that, in the investigator's judgment, make the patient unsuitable for study enrollment, completion of the study, or follow-up.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Diagnostic

Study locations

China · 1 center

• Chuanbao Li — Jinan

Publications

• Gulati M, Levy PD, Mukherjee D, Amsterdam E, Bhatt DL, Birtcher KK, Blankstein R, Boyd J, Bullock-Palmer RP, Conejo T, Diercks DB, Gentile F, Greenwood JP, Hess EP, Hollenberg SM, Jaber WA, Jneid H, Joglar JA, Morrow DA, O'Connor RE, Ross MA, Shaw LJ. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/Ameri PMID 34709879
• Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, Pope JH, Hauser TH, White CS, Weiner SG, Kalanjian S, Mullins ME, Mikati I, Peacock WF, Zakroysky P, Hayden D, Goehler A, Lee H, Gazelle GS, Wiviott SD, Fleg JL, Udelson JE; ROMICAT-II Investigators. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012 Jul 26;367(4):299-308. doi: 10.1056/N PMID 22830462
• Gongora CA, Bavishi C, Uretsky S, Argulian E. Acute chest pain evaluation using coronary computed tomography angiography compared with standard of care: a meta-analysis of randomised clinical trials. Heart. 2018 Feb;104(3):215-221. doi: 10.1136/heartjnl-2017-311647. Epub 2017 Aug 30. PMID 28855273
• Foy AJ, Dhruva SS, Peterson B, Mandrola JM, Morgan DJ, Redberg RF. Coronary Computed Tomography Angiography vs Functional Stress Testing for Patients With Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis. JAMA Intern Med. 2017 Nov 1;177(11):1623-1631. doi: 10.1001/jamainternmed.2017.4772. PMID 28973101
• SCOT-HEART Investigators; Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, Hunter A, Lewis S, MacLean S, Mills NL, Norrie J, Roditi G, Shah ASV, Timmis AD, van Beek EJR, Williams MC. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018 Sep 6;379(10):924-933. doi: 10.1056/NEJMoa1805971. Epub 2018 Aug 25. PMID 30145934
• Moss AJ, Williams MC, Newby DE, Nicol ED. The Updated NICE Guidelines: Cardiac CT as the First-Line Test for Coronary Artery Disease. Curr Cardiovasc Imaging Rep. 2017;10(5):15. doi: 10.1007/s12410-017-9412-6. Epub 2017 Mar 27. PMID 28446943
• Goodacre S, Thokala P, Carroll C, Stevens JW, Leaviss J, Al Khalaf M, Collinson P, Morris F, Evans P, Wang J. Systematic review, meta-analysis and economic modelling of diagnostic strategies for suspected acute coronary syndrome. Health Technol Assess. 2013;17(1):v-vi, 1-188. doi: 10.3310/hta17010. PMID 23331845
• Mowatt G, Cummins E, Waugh N, Walker S, Cook J, Jia X, Hillis GS, Fraser C. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease. Health Technol Assess. 2008 May;12(17):iii-iv, ix-143. doi: 10.3310/hta12170. PMID 18462576

Identifiers

NCT: NCT07140419 · KYLL-202412(XZ)-014-3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗