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

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Major Adverse Cardiovascular Events (MACE) [Time frame: At 1 year (365 days) post-AVR]

Secondary outcome measures (4)

• Incidence of All-Cause Mortality at 1 Year [Time frame: At 1 year (365 days) post-AVR]
• Incidence of All-Cause Mortality at 30 Days [Time frame: At 30 days post-AVR]
• Incidence of Patient-Oriented Composite Endpoint at 1 Year [Time frame: At 1 year (365 days) post-AVR]
• Incidence of Patient-Oriented Composite Endpoint at 30 Days [Time frame: At 30 days post-AVR]

Eligibility criteria

Inclusion criteria

• Age >18 years.
• 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 \[or indexed aortic valve area (AVAi) ≤0.6 cm²/m²\].
• New York Heart Association (NYHA) functional class II or higher.
• Eligible for both transfemoral transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).
• Undergoing preoperative coronary computed tomography angiography (CCTA).
• Willing to participate in the study and able to provide written informed consent.

Exclusion criteria

• Allergy to prosthetic valve materials or iodinated contrast agents.
• Contraindication or allergic reaction to anticoagulants or antiplatelet agents, or inability to tolerate required anticoagulant or antiplatelet therapy.
• Active infective endocarditis or any other active infection.
• Severe vascular disease precluding safe implantation of a prosthetic valve.
• Ascending aortic diameter ≥50 mm.
• Prior prosthetic valve implantation in any cardiac position or prior coronary artery bypass grafting (CABG).
• Preoperative imaging confirming aortic root anatomy unsuitable for transcatheter aortic valve implantation.
• Intracardiac mass, left ventricular or left atrial thrombus, or vegetation confirmed by preoperative echocardiography.
• Acute myocardial infarction within 30 days before surgery.
• Clinically diagnosed stroke or transient ischemic attack within 3 months before surgery.
• 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.

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

Treatment

Study locations

China · 1 center

• Yan'an Hospital Affiliated to Kunming Medical University — Kunming

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 Tom PMID 36436841
• 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 P PMID 33342587
• 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 PMID 40878295

Identifiers

NCT: NCT07469371 · 2025-412-01 · 2026Y0391

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗