Clinical Outcomes of CT-FFR Versus QFR-guided Strategy for Decision-Making in Patients With Stable Chest Pain (CONFIDENT)

Clinical Outcomes of CoroNary CTA-Derived FFR Versus ICA-Derived QFR-guided Strategy for Decision-Making in Patients With Stable Chest Pain

This study is a multicenter, prospective, blinded (blinding of clinical evaluators), randomized controlled, event-driven non-inferiority clinical trial. Eligible subjects who meet the inclusion criteria will be registered in the central randomization system and randomized in a 1:1 ratio to either the experimental group (CT-FFR guided group) or the control group (QFR guided group).

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Angina, Stable
• Intervention / Treatment: Device: CT-FFR; Device: QFR

Detailed Description

This study is a multicenter, prospective, blinded, randomized controlled trial with event-driven non-inferiority design (blinding of clinical evaluators). A total of 4,648 participants will be recruited and randomly assigned to the CT-FFR guided group or the QFR guided group in a 1:1 ratio. Patients in the experimental group (CT-FFR guided group) will undergo three-dimensional reconstruction of coronary arteries and CT-FFR calculation using coronary CT angiography (CCTA) images and the RuiXin-FFR software. The CT-FFR results will be interpreted and analyzed by the researchers. If the CT-FFR value is >0.8, patients will receive medical therapy only, while if the CT-FFR value is ≤0.8, patients will undergo further coronary angiography to determine the appropriate treatment strategy (PCI, CABG, or medical therapy), based on the anatomical features of the lesion and CT-FFR results. Patients in the control group (QFR guided group) will undergo invasive coronary angiography (ICA) and QFR calculation based on ICA images. If the QFR value is ≤0.8 and the lesion is suitable for intervention, patients will receive PCI, while if the QFR value is >0.8, medical therapy will be recommended. Both groups will be followed up for clinical outcomes, health economics indicators, and quality of life at 1 month, 6 months, 1 year, 2 years, and 3 years. The occurrence of major adverse cardiovascular events (MACE) will be compared between the two groups. The study will also assess the effectiveness, safety, and economic value of CT-FFR in guiding diagnosis and treatment decisions for patients with stable angina, using QFR guided PCI as a control, with a non-inferiority comparison.

• Study Type: Interventional
• Enrollment (Anticipated): 4648
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: chenguang Li, doctor; Phone Number: 13816767665; Email: li.chenguang@zs-hospital.sh.cn

Study Locations

• China
  • Shagnhai
    • Shanghai, Shagnhai, China, 200032
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• with stable chest pain who underwent CCTA and have at least 1 lesion with a percent diameter stenosis (DS%) between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment.These patients plan to undergo further non-invasive or invasive diagnosis and treatment.
• Able to undergo invasive coronary angiography (ICA)
• Capable of complying with the study procedures and fully understand the informed consent form approved by the ethics committee, and provide voluntary consent.

Exclusion Criteria:

General exclusion criteria:

• Patients with acute coronary syndrome requiring urgent revascularization.
• Patients with unstable angina, including those with first-onset chest pain within 48 hours, CCS III or higher first-onset angina, those whose angina has worsened to CCS III or IV within a short period of time, or those with rest angina lasting more than 20 minutes.
• Patients with iodine contrast agent allergy.
• Pregnant or lactating women.
• Patients with severe congestive heart failure (NYHA III-IV or LVEF <30%) or acute pulmonary edema.
• Patients with severe renal insufficiency (creatinine >150μmol/L or estimated - -glomerular filtration rate calculated by the Cockcroft-Gault formula <45ml/kg/1.73 m2).
• Patients with other comorbidities and an expected survival time of less than 1 year.
• Patients who, for any other reason, are considered by the investigators to be unsuitable for inclusion in the study or unable to complete the study and follow-up.

Coronary CTA and coronary angiography exclusion criteria:

• Patients with a body mass index >35 when undergoing coronary CT testing, resulting in poor CT image quality due to motion artifacts, severe calcification, or inadequate iodine contrast agent filling.
• Patients with a history of coronary artery bypass grafting (CABG).
• Target lesions related to acute myocardial infarction.
• Target lesions involving left main stem disease.
• Target lesions involving myocardial bridging.
• Target lesions involving in-stent restenosis.
• Low-quality angiography due to poor visualization of vascular boundaries or poor iodine contrast agent filling.
• Excessive overlap of the stenotic segment or severe tortuosity of the target vessel, making QFR calculation impossible.

Regen

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT-FFR guided group; Patients randomized to the experimental group (CT-FFR guided group) will undergo coronary artery three-dimensional reconstruction and CT-FFR calculation using the coronary CT angiography (CCTA) images and RuiXin-FFR software. The researchers will interpret and analyze the clinical outcomes based on CT-FFR results. If CT-FFR is >0.8, the patient will be treated with medical therapy alone. If CT-FFR is ≤0.8, further examination with coronary angiography will be performed. During the angiography examination, the operator will determine the treatment strategy (PCI, CABG, or medical therapy alone) based on the anatomical features of the lesion and the CT-FFR results.	Device: CT-FFR; CT -FFR(coronary computed tomography angiography drived fractional flow reserve derived) uses routine coronary computed tomography angiography (CTA) images and applies a specific algorithm to extract both anatomical and physiological information of the coronary arteries. By combining these two pieces of information, a fluid dynamics model of the coronary arteries can be established, allowing the calculation of FFR at any location of the coronary arteries.
Active Comparator: QFR guided group; Patients randomized to the control group (QFR-guided group) will undergo invasive coronary angiography (ICA) in the catheterization lab, and QFR will be calculated using the ICA images. The researchers will interpret and analyze the clinical outcomes based on QFR results. If QFR is ≤0.8 and the lesion is suitable for intervention, the patient will undergo percutaneous coronary intervention (PCI) treatment. If QFR is >0.8, the patient will be recommended for medical treatment alone.	Device: QFR; Quantitative flow ratio (QFR) is a new method for evaluating the functional significance of coronary artery stenosis based on angiography. It can be used for real-time detection of hemodynamic abnormalities in the coronary arteries in the catheterization lab. Unlike traditional methods that require the use of pressure wires and vasodilators such as adenosine, the QFR examination process only requires routine coronary angiography. By reconstructing the three-dimensional structure of the blood vessels and analyzing the hemodynamics, the QFR can evaluate the fractional flow reserve (FFR) without the need for pressure wires and vasodilators.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year MACE	Major Adverse Coronary Event (MACE) rates, defined as: All cause death; myocardial infarction (MI); Repeat myocardial revascularization; non-lethal stroke	1-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	Major Adverse Coronary Event (MACE) rates, defined as: All cause death; myocardial infarction (MI); Repeat myocardial revascularization; non-lethal stroke	1-month, 6-month, 2-years, 3-years
All cause death	All cause death defined as: Cardiovascular death, non-cardiovascular death, death of unknown cause	1-month, 6-month, 1-year, 2-years, 3-years
Non-fatal myocardial infarction (MI)	myocardial infarction (MI) defined as: Spontaneous myocardial infarction , perioperative myocardial infarction	1-month, 6-month, 1-year, 2-years, 3-years
repeat myocardial	Repeat myocardial defined as:Planned revascularization,Unplanned revascularization	1-month, 6-month, 1-year, 2-years, 3-years
non-lethal stroke	The American Heart Association/American Stroke Association (AHA/ASA) defines stroke as including the following types:CNS infarction,Ischemic stroke,Silent CNS infarction,Intracerebral hemorrhage,Subarachnoid hemorrhage,Cerebral venous thrombosis	1-month, 6-month, 1-year, 2-years, 3-years
The definite and probable stent thrombosis (defined by ARC-2 criteria)	The definite and probable stent thrombosis (defined by ARC-2 criteria) including acute, subacute, late, and very late stent thrombosis within a specific time frame.	1-month, 6-month, 1-year, 2-years, 3-years
Proportion of non-obstructive CAD detected by ICA examination	Proportion of non-obstructive CAD detected by ICA examination	1-month, 6-month, 1-year, 2-years, 3-years
Health Economics Evaluation Endpoints	Cost-effectiveness analysis, cost-utility analysis. The information collected by the cost indicators is as follows: Costs associated with initial hospitalization, including:; Estimated cost of major cardiovascular medication; Total medical expenses related to major cardiac adverse events occurring during outpatient and/or hospitalization	1-month, 6-month, 1-year, 2-years, 3-years
Quality of life (QOL)	Quality of life (QOL) will be assessed using the EQ-5D-VAS questionnaire. Angina status will be assessed using the Seattle Angina Questionnaire.	1-month, 6-month, 1-year, 2-years, 3-years
Cumulative radiation exposure	Cumulative radiation exposure within1-month, 6-month, 1-year, 2-years and 3-years of study entry included all cardiovascular tests and invasive procedures, including CTA, myocardial perfusion imaging, and ICA.	1-month, 6-month, 1-year, 2-years, 3-years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Study Chair: Junbo Ge, Doctor, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): May 1, 2028

Study Registration Dates

• First Submitted: April 22, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Angina Pectoris; Coronary Artery Disease; Chest Pain; Angina, Stable
• Other Study ID Numbers: RX-RD-FFR-FA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No