Invasive Versus Non-invasive Approach in Symptomatic Patient With Non-High Risk Coronary Artery Stenosis (SMART-STEP)

November 19, 2025 updated by: Joo Myung Lee, Samsung Medical Center

Invasive Versus Non-invasive Approach in Symptomatic Patients With Non-High Risk Coronary Artery Stenosis (SMART-STEP Trial)

A pragmatic, prospective, multi-center, open label, randomized controlled, superiority trial.

The study will compare clinical outcomes between invasive versus non-invasive approach as next diagnostic step in symptomatic patients with non-high risk obstructive coronary artery disease (CAD) on coronary computed tomography-angiography (CCTA).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CCTA has been emerged as useful diagnostic tool to evaluate CAD. Besides high diagnostic accuracy, CCTA has additional benefit of measuring the cumulative atherosclerotic burden and more accurately discriminating obstructive CAD with additional fractional flow reserve by CT (FFRCT), making it more predictive of a patient's prognosis. Recently, several randomized clinical trials have demonstrated the clinical utility of CCTA when compared with noninvasive stress test, which has been previously widely used as an initial assessment for stable chest pain, or invasive coronary angiography, which is the gold standard for diagnosing obstructive CAD.

On this background, CCTA, along with stress imaging test, is recommended as first step to diagnose obstructive CAD in patients with intermediate to high pretest probabilities with stable chest pain and is increasingly utilized. Although CCTA is increasingly used as initial assessment tool in these patients, there are insufficient studies to clearly establish the next step after obstructive CAD is confirmed in CCTA. Without high-risk features of CAD on CCTA, current guidelines suggest noninvasive stress imaging or FFRCT as class IIA recommendation. However, supporting evidence of these suggestions are mostly based on studies with low level of evidence. Furthermore, given the limited diagnostic performance of noninvasive stress test, concern remains whether it is safe to defer invasive coronary angiography based on the result from noninvasive stress test in patients with obstructive CAD on CCTA.

Therefore, this trial aims to compare clinical outcomes between invasive versus non-invasive approach as next diagnostic step in symptomatic patients with non-high risk obstructive CAD on CCTA.

Study Type

Interventional

Enrollment (Estimated)

2000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • South Korea
      • Bucheon-si, South Korea
        • Recruiting
        • Soonchunhyang University Hospital Bucheon
        • Contact:
        • Principal Investigator:
          • Jon Suh, MD, PhD
      • Chuncheon, South Korea
        • Recruiting
        • Kangwon National University Hospital
        • Contact:
        • Principal Investigator:
          • Byung Ryul Cho, MD, PhD
      • Chungju, South Korea
        • Recruiting
        • Chungbuk National University Hospital
        • Contact:
        • Principal Investigator:
          • Woong Gil Choi, MD, PhD
      • Daegu, South Korea
        • Recruiting
        • Keimyung University Dongsan Medical Center
        • Contact:
        • Principal Investigator:
          • Hyuck Jun Yoon, MD,PhD
      • Daegu, South Korea
        • Recruiting
        • Kyungpook National University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jang Hoon Lee, MD, PhD
        • Sub-Investigator:
          • Namkyun Kim, MD, PhD
      • Daejeon, South Korea
        • Recruiting
        • Chungnam National University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Pil Sang Song, MD, PhD
        • Sub-Investigator:
          • Jin-Ok Jeong, MD, PhD
      • Gwangju, South Korea
        • Recruiting
        • Chonnam National University
        • Contact:
        • Sub-Investigator:
          • Seung Hun Lee, MD, PhD
        • Contact:
        • Principal Investigator:
          • Young Joon Hong, MD, PhD
      • Gwangmyeong, South Korea
        • Recruiting
        • Chung-Ang University Gwangmyeong Hospital
        • Contact:
        • Principal Investigator:
          • Sang Yeub Lee, MD, PhD
      • Ilsan, South Korea
        • Recruiting
        • Inje University Ilsan Paik Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Joonhyung Doh, MD, PhD
        • Sub-Investigator:
          • Sung Eun Kim, MD, PhD
      • Incheon, South Korea
        • Recruiting
        • Gachon University Gil Medical Center
        • Contact:
        • Principal Investigator:
          • Seung Hwan Han, MD, PhD
      • Incheon, South Korea
        • Recruiting
        • Kwandong University Intl. ST. Mary's Hospital
        • Contact:
        • Principal Investigator:
          • Hyung-Bok Park, MD, PhD
      • Jinju, South Korea
        • Recruiting
        • Gyeongsang National University Hospital
        • Contact:
        • Principal Investigator:
          • Hangyul Kim, MD, PhD
        • Contact:
        • Sub-Investigator:
          • Jin Sin Koh, MD, PhD
      • Seongnam-si, South Korea
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
        • Principal Investigator:
          • Ki-Hyun Jeon, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Chung-Ang University Hospital
        • Contact:
        • Principal Investigator:
          • Ho Youn Won, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Ewha Womans University Mokdong Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kyung-Jin Kim, MD, PhD
        • Sub-Investigator:
          • So-Dam Jung, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Samsung Medical Center
        • Principal Investigator:
          • Joo Myung Lee, MD, MPH, PhD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • David Hong, MD
      • Seoul, South Korea
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
        • Principal Investigator:
          • Soon-Jun Hong, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Seoul National University Boramae Medical Center
        • Contact:
        • Principal Investigator:
          • Hyun Sung Joh, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Ewha Womans University Seoul Hospital
        • Contact:
        • Principal Investigator:
          • Sang Hoon Shin, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Hanyang University Seoul Hospital, College of Medicine, Hanyang University
        • Contact:
        • Principal Investigator:
          • Young-Hyo Lim, MD, PhD
      • Seoul, South Korea
        • Recruiting
        • Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
        • Contact:
        • Principal Investigator:
          • Jong-Young Lee, MD, PhD
        • Sub-Investigator:
          • Seung-Jae Lee, MD, PhD
        • Sub-Investigator:
          • Woochan Kwon, MD, PhD
        • Contact:
      • Suwon, South Korea
        • Recruiting
        • Ajou University Hospital
        • Contact:
        • Principal Investigator:
          • Hong-Seok Lim, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subject age ≥19 years old
  2. Patients with new or worsening chest pain syndrome, equivalent symptoms, or abnormal laboratory test findings (suspected ischemic changes in electrocardiography, regional wall motion abnormality in echocardiography, or coronary calcium score > 100) suspected for clinically significant CAD who are evaluated by CCTA
  3. Any other clinical circumstance in which physician judged to proceed CCTA
  4. Obstructive CAD in CCTA (≥50% diameter stenosis)
  5. Subject who can verbally confirm understandings of risks, benefits, and treatment alternatives of receiving invasive approach and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.

Exclusion Criteria:

  1. Diagnosed or suspected acute coronary syndrome (ACS) requiring hospitalization or urgent or emergent testing (elevated cardiac troponin or CK-MB)
  2. High risk CAD (left main stenosis ≥ 50%; anatomically significant 3-vessel disease with ≥70% stenosis)
  3. Hemodynamically or clinically unstable condition (systolic BP < 90 mmHg, ventricular arrhythmias, or persistent resting chest pain in ischemic nature despite adequate therapy
  4. Known CAD with previous MI, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG)
  5. Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic shock)
  6. Known significant congenital, severe valvular or cardiomyopathic (hypertrophic or dilated cardiomyopathy, or any other forms) process which could explain cardiac symptoms.
  7. Severe left ventricular systolic dysfunction (ejection fraction <30%)
  8. Intolerance to Aspirin, Clopidogrel, or Heparin.
  9. Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may result in protocol non-compliance (per site investigator's medical judgment)
  10. Unwillingness or inability to comply with the procedures described in this protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Invasive approach group
Invasive coronary angiography will be performed as next diagnostic step in symptomatic patients with non-high risk obstructive CAD on CCTA..
Diagnostic test: Invasive coronary angiography
As alternative to non-invasive functional testing, invasive coronary angiography will be performed.
Active Comparator: Non-invasive approach group
Usual care of non-invasive ischemia testing (exercise electrocardiography [ECG], stress echocardiography by exercise or pharmacologic agent, nuclear test including SPECT or PET, stress cardiac magnetic resonance [MR]) will be performed as next diagnostic step in symptomatic patients with non-high risk obstructive CAD on CCTA.
Diagnostic test: Non-invasive functional test
Standard non-invasive functional testing will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first event of major adverse cardiac events (MACE)
Time Frame: 2 years after the last patient enrollment
MACE is a composite of death from any causes, myocardial infarction (MI), clinically driven unplanned revascularization.
2 years after the last patient enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause death
Time Frame: 2 years after the last patient enrollment
All-cause death
2 years after the last patient enrollment
Cardiac death
Time Frame: 2 years after the last patient enrollment
Cardiac death
2 years after the last patient enrollment
Any MI
Time Frame: 2 years after the last patient enrollment
Defined by Forth Universal definition of MI
2 years after the last patient enrollment
Spontaneous MI
Time Frame: 2 years after the last patient enrollment
Defined by Forth Universal definition of MI
2 years after the last patient enrollment
Procedure-related MI
Time Frame: 2 years after the last patient enrollment
Defined by ARC II definition
2 years after the last patient enrollment
Resuscitated cardiac arrest
Time Frame: 2 years after the last patient enrollment
Resuscitated cardiac arrest
2 years after the last patient enrollment
Unplanned revascularization (clinically driven)
Time Frame: 2 years after the last patient enrollment
Unplanned revascularization (clinically driven)
2 years after the last patient enrollment
Rate of index coronary angiography
Time Frame: up to 30 days following randomization
Rate of index coronary angiography
up to 30 days following randomization
Rate of index revascularization by PCI or CABG
Time Frame: up to 30 days following randomization
Rate of index revascularization by PCI or CABG
up to 30 days following randomization
European Quality of Life-5 Dimensions
Time Frame: 6 months after initial management according to allocated diagnostic test
European Quality of Life-5 Dimensions
6 months after initial management according to allocated diagnostic test
Seattle Angina Questionnaire
Time Frame: 6 months after initial management according to allocated diagnostic test
Seattle Angina Questionnaire
6 months after initial management according to allocated diagnostic test
Total medical cost
Time Frame: 2 years after the last patient enrollment
Total medical cost
2 years after the last patient enrollment
Procedure-related complications from invasive procedure
Time Frame: up to 30 days following randomization
Procedure-related complications from invasive procedure
up to 30 days following randomization
Cerebrovascular accidents
Time Frame: 2 years after the last patient enrollment
Cerebrovascular accidents (ischemic or hemorrhagic)
2 years after the last patient enrollment
Major adverse cardiac and cerebrovascular events
Time Frame: 2 years after the last patient enrollment
Major adverse cardiac and cerebrovascular events (MACCE, a composite of death, MI, clinically-driven unplanned revascularization, or cerebrovascular accident)
2 years after the last patient enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Investigators

  • Principal Investigator: Joo Myung Lee, MD, MPH, PhD, Samsung Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 2, 2023

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

March 22, 2023

First Submitted That Met QC Criteria

April 4, 2023

First Posted (Actual)

April 5, 2023

Study Record Updates

Last Update Posted (Actual)

November 20, 2025

Last Update Submitted That Met QC Criteria

November 19, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SMC2023-02-096-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked

IPD Sharing Time Frame

After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked

IPD Sharing Access Criteria

After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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