CLEAR-AS: CT-FFR-Guided Revascularization in Patients With Severe Aortic Stenosis (CLEAR-AS)

CT-FFR-Guided Revascularization in Patients With Severe Aortic Stenosis: A Randomized Controlled Trial

Severe aortic stenosis (AS) is often accompanied by coronary artery disease (CAD). While coronary computed tomography angiography (CCTA) is routinely used before aortic valve replacement (AVR) to evaluate coronary anatomy, it lacks physiological assessment of myocardial ischemia.

This prospective, single-center, randomized controlled trial aims to evaluate whether integrating functional assessment using CT-derived fractional flow reserve (CT-FFR) with CCTA can optimize revascularization decision-making and improve clinical outcomes. A total of 300 severe AS patients scheduled for transcatheter or surgical AVR will be randomly assigned to either the experimental group (revascularization decisions guided by both CCTA and CT-FFR) or the control group (decisions guided by CCTA alone). Participants will be followed up for 1 year to assess major adverse cardiovascular events and other clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Severe Aortic Stenosis
• Intervention / Treatment: Other: CCTA plus CT-FFR-informed preoperative decision strategy; Other: CCTA-guided preoperative decision strategy

Detailed Description

Patients with severe aortic stenosis (AS) frequently have concomitant coronary artery disease (CAD), which complicates pre-operative evaluation and clinical decision-making for transcatheter (TAVR) or surgical aortic valve replacement (SAVR). Although coronary computed tomography angiography (CCTA) provides excellent anatomical evaluation and has become a standard pre-AVR workflow, it is insufficient for determining the functional and hemodynamic significance of coronary lesions. CT-derived fractional flow reserve (CT-FFR) offers a novel, non-invasive method to evaluate the ischemic burden.

The objective of this prospective, single-center, randomized, parallel-controlled trial is to determine whether a "functional + anatomical" assessment strategy using CT-FFR provides incremental value over an "anatomical-only" strategy.

A total of 300 eligible patients with severe AS planned for AVR will be randomized in a 1:1 ratio into two groups:

1. Experimental Group (CCTA + CT-FFR): The Heart Team will formulate the revascularization strategy (e.g., concomitant or staged PCI/CABG) based on both CCTA anatomical stenosis and CT-FFR physiological data (using a threshold of CT-FFR ≤0.80 to define hemodynamically significant ischemia).
2. Active Comparator Group (CCTA alone): The Heart Team will formulate the revascularization strategy based solely on CCTA anatomical grading according to the CAD-RADS classification.

All participants will be followed for 365 days post-AVR. The primary endpoint is a patient-oriented composite of major adverse cardiovascular events (MACE, including nonfatal myocardial infarction, unstable angina, cardiac death, or heart failure admission), disabling stroke, clinically-driven target vessel revascularization, valve re-intervention, and life-threatening or disabling bleeding. The study hypothesizes that incorporating CT-FFR into routine pre-AVR evaluation will optimize concomitant revascularization decisions, avoid unnecessary invasive procedures, and ultimately reduce the risk of post-operative adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xirui Duan; Phone Number: +86 13294957739; Email: 248190836@qq.com

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650050
      • Recruiting
      • Yan'an Hospital Affiliated to Kunming Medical University
      • Contact: Xirui Duan; Phone Number: +86 13294957739; Email: 248190836@qq.com
      • Contact: Chengde Liao; Phone Number: +86 13888040671; Email: chengdeliao@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age >18 years.
2. Severe aortic stenosis confirmed by echocardiography, defined as peak aortic jet velocity (Vmax) ≥4.0 m/s, mean transvalvular gradient ≥40 mmHg, or aortic valve area (AVA) ≤1.0 cm² [or indexed aortic valve area (AVAi) ≤0.6 cm²/m²].
3. New York Heart Association (NYHA) functional class II or higher.
4. Eligible for both transfemoral transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).
5. Undergoing preoperative coronary computed tomography angiography (CCTA).
6. Willing to participate in the study and able to provide written informed consent.

Exclusion Criteria:

1. Allergy to prosthetic valve materials or iodinated contrast agents.
2. Contraindication or allergic reaction to anticoagulants or antiplatelet agents, or inability to tolerate required anticoagulant or antiplatelet therapy.
3. Active infective endocarditis or any other active infection.
4. Severe vascular disease precluding safe implantation of a prosthetic valve.
5. Ascending aortic diameter ≥50 mm.
6. Prior prosthetic valve implantation in any cardiac position or prior coronary artery bypass grafting (CABG).
7. Preoperative imaging confirming aortic root anatomy unsuitable for transcatheter aortic valve implantation.
8. Intracardiac mass, left ventricular or left atrial thrombus, or vegetation confirmed by preoperative echocardiography.
9. Acute myocardial infarction within 30 days before surgery.
10. Clinically diagnosed stroke or transient ischemic attack within 3 months before surgery.
11. Bleeding or coagulation disorders within 3 months before surgery that required hospitalization or blood transfusion or were otherwise clinically significant and would preclude the antiplatelet therapy required in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CCTA + CT-FFR Group; Preoperative revascularization decision-making (TAVR/SAVR) is guided by both CCTA anatomical information and CT-FFR functional information.	Other: CCTA plus CT-FFR-informed preoperative decision strategy; Preoperative coronary evaluation and revascularization decision-making before aortic valve replacement are based on combined CCTA anatomical assessment and CT-FFR functional assessment. When anatomical and functional assessments are concordant, both are considered in treatment planning. When anatomical and functional assessments are discordant, the CT-FFR functional result serves as the primary basis for revascularization decision-making.
Active Comparator: CCTA Group; Preoperative revascularization decision-making (TAVR/SAVR) is guided solely by CCTA anatomical information.	Other: CCTA-guided preoperative decision strategy; CCTA is performed as the standardized preoperative anatomic coronary assessment in patients with severe aortic stenosis scheduled for aortic valve replacement. Coronary stenosis is evaluated by 2 experienced radiologists using the 18-segment coronary model, visual diameter stenosis assessment, and CAD-RADS 2.0 classification. In the control strategy, coronary evaluation and revascularization planning are based on CCTA anatomic findings alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiovascular Events (MACE)	The primary endpoint is a cardiovascular-focused composite including major adverse cardiovascular events (MACE, defined as cardiac death, nonfatal myocardial infarction, unstable angina, heart failure admission, clinically-driven target vessel revascularization, or valve re-intervention). This outcome will be reported as the percentage of participants experiencing at least one of these events.	At 1 year (365 days) post-AVR

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of All-Cause Mortality at 1 Year	The rate of death from any cause, including both cardiac and non-cardiac deaths. Reported as the percentage of participants.	At 1 year (365 days) post-AVR
Incidence of All-Cause Mortality at 30 Days	The rate of early death from any cause (cardiac and non-cardiac). Reported as the percentage of participants.	At 30 days post-AVR
Incidence of Patient-Oriented Composite Endpoint at 1 Year	The composite of MACE (nonfatal myocardial infarction, unstable angina, cardiac death, or heart failure admission), disabling stroke, clinically-driven target vessel revascularization, valve re-intervention, and life-threatening or disabling bleeding occurring within the early post-operative period.	At 1 year (365 days) post-AVR
Incidence of Patient-Oriented Composite Endpoint at 30 Days	The composite of MACE (nonfatal myocardial infarction, unstable angina, cardiac death, or heart failure admission), disabling stroke, clinically-driven target vessel revascularization, valve re-intervention, and life-threatening or disabling bleeding occurring within the early post-operative period .	At 30 days post-AVR

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome: Rate of Concomitant or Staged Coronary Revascularization	An exploratory procedural endpoint defined as the proportion of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) concomitantly at the time of aortic valve replacement (AVR), and/or staged PCI/CABG performed within 30 days prior to AVR. This endpoint is included to capture the clinical decision-making pathway and the real-world impact of the preoperative assessment strategy. Reported as the percentage of participants.	Up to 30 days prior to AVR and at the time of the AVR procedure

Collaborators and Investigators

• Sponsor: Yan'an Affiliated Hospital of Kunming Medical University
• Investigators: Principal Investigator: Chengde Liao, Yan'an Affiliated Hospital of Kunming Medical University

Publications and helpful links

General Publications

• Cury RC, Leipsic J, Abbara S, Achenbach S, Berman D, Bittencourt M, Budoff M, Chinnaiyan K, Choi AD, Ghoshhajra B, Jacobs J, Koweek L, Lesser J, Maroules C, Rubin GD, Rybicki FJ, Shaw LJ, Williams MC, Williamson E, White CS, Villines TC, Blankstein R. CAD-RADS 2.0 - 2022 Coronary Artery Disease - Reporting and Data System.: An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the American College of Radiology (ACR) and the North America Society of Cardiovascular Imaging (NASCI). J Am Coll Radiol. 2022 Nov;19(11):1185-1212. doi: 10.1016/j.jacr.2022.09.012.
• Writing Committee Members; Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2021 Feb 2;77(4):450-500. doi: 10.1016/j.jacc.2020.11.035. Epub 2020 Dec 17.
• Praz F, Borger MA, Lanz J, Marin-Cuartas M, Abreu A, Adamo M, Ajmone Marsan N, Barili F, Bonaros N, Cosyns B, De Paulis R, Gamra H, Jahangiri M, Jeppsson A, Klautz RJM, Mores B, Perez-David E, Poss J, Prendergast BD, Rocca B, Rossello X, Suzuki M, Thiele H, Tribouilloy CM, Wojakowski W; ESC/EACTS Scientific Document Group. 2025 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2025 Nov 21;46(44):4635-4736. doi: 10.1093/eurheartj/ehaf194. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: 2025-412-01; 2026Y0391 (Other Grant/Funding Number: Department of Education of Yunnan Province)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data sharing has not yet been determined. The study team will decide after completion of the trial, database lock, and review of applicable ethical, privacy, and institutional requirements.

Drug and device information, study documents

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