Computed Tomography Angiography Based Procedural Planning in PeRcutaneOus Coronary InterVEntion

CT-PROVE: Computed Tomography Angiography Based Procedural Planning in PeRcutaneOus Coronary InterVEntion

The goal of this clinical trial is to learn whether coronary CT angiography (CCTA)-guided planning improves the efficiency and outcomes of percutaneous coronary intervention (PCI) in adults with coronary artery disease. It will also evaluate the feasibility and safety of using a CT-based "virtual PCI plan" during coronary interventions.

The main questions it aims to answer are:

• Does CCTA-guided PCI reduce procedural time, radiation exposure, and contrast dye use compared with standard PCI?
• Does CCTA-guided PCI improve procedural outcomes and stent optimization?
• How often do operators follow or deviate from the CT-based procedural plan?
• What medical problems or complications occur during and after CCTA-guided PCI?

Researchers will compare CCTA-guided PCI with standard angiography-guided PCI to determine whether CT-derived procedural planning improves PCI efficiency and clinical outcomes.

Participants will:

• Undergo PCI guided either by a CCTA-based virtual planning strategy or by standard clinical practice
• Attend follow-up assessments at 1 month, 6 months, and 1 year
• Undergo routine clinical evaluations and imaging assessments related to their PCI procedure
• Be monitored for procedural complications, symptoms, repeat procedures, and cardiovascular outcomes during follow-up

The study will also include a parallel observational registry for patients whose coronary lesions are deferred from PCI, to evaluate their long-term clinical outcomes.

Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality worldwide. Percutaneous coronary intervention (PCI) is routinely performed to treat obstructive CAD; however, conventional invasive coronary angiography provides limited information regarding plaque morphology, lesion composition, calcium distribution, vessel remodeling, and functional lesion significance. These limitations may affect procedural planning, device selection, procedural efficiency, and final PCI optimization.

Coronary computed tomography angiography (CCTA) has evolved into a comprehensive non-invasive imaging modality capable of providing detailed anatomical and functional assessment of coronary lesions. In addition to defining stenosis severity, CCTA allows assessment of lesion length, vessel dimensions, plaque morphology, high-risk plaque characteristics, calcium burden, bifurcation anatomy, and vessel trajectory. Furthermore, computational fluid dynamics enable the derivation of CT-based fractional flow reserve (CT-FFR), providing a non-invasive estimation of lesion-specific ischemia.

The CT-PROVE trial (Computed Tomography Angiography Based Procedural Planning in PeRcutaneOus Coronary InterVEntion) is a prospective, multicenter, randomized, controlled, open-label clinical trial designed to evaluate the implementation of a CCTA-derived virtual PCI planning strategy during invasive coronary intervention. The study aims to determine whether integrating a structured CT-based procedural planning workflow into PCI practice improves procedural efficiency and procedural outcomes compared with standard angiography-guided PCI.

Patients with chronic coronary syndrome or stabilized acute coronary syndrome who undergo clinically indicated CCTA and are subsequently referred for invasive coronary angiography will be screened for enrollment. Eligible patients presenting with at least one target lesion meeting predefined anatomical and/or functional criteria on CCTA will be considered for inclusion.

The study consists of two randomized groups:

1. CCTA-Guided PCI Group (Interventional Arm)
2. Standard PCI Group (Control Arm)

Patients randomized to the interventional arm will undergo PCI guided by a detailed pre-procedural CCTA-based virtual planning strategy. The virtual planning will be generated centrally by the core laboratory at Galway University Hospital using advanced anatomical and functional CT analysis software. The planning workflow includes evaluation of:

• Coronary anatomy and vessel course
• Optimal angiographic projections
• Lesion length
• Proximal and distal landing zones
• Reference vessel dimensions
• Calcium burden and distribution
• Plaque morphology and high-risk plaque features
• Bifurcation anatomy and side branch characteristics
• CT-derived fractional flow reserve (CT-FFR)

Based on these analyses, operators will receive a structured procedural recommendation including suggested guiding catheter support, lesion preparation strategy, calcium modification techniques if necessary, stent sizing, landing zones, and bifurcation management approach.

Patients randomized to the control arm will undergo PCI according to standard clinical practice and operator discretion. Operators in the control arm will remain blinded to the advanced CCTA-derived procedural planning throughout the intervention. Use of intravascular imaging, physiological assessment, and adjunctive devices will be permitted according to standard care and operator judgment.

The primary objective of the study is to assess the efficiency and feasibility of integrating a CCTA-based PCI planning strategy into routine catheterization laboratory workflow.

Primary efficiency endpoints include:

• Procedural time
• Radiation exposure during PCI
• Contrast volume utilization

A co-primary feasibility endpoint will assess the rate of deviation between the recommended CCTA-based virtual procedural plan and the PCI procedure actually performed by the operator.

Secondary objectives include evaluating the effect of CCTA-guided PCI on:

• Procedural optimization
• Functional revascularization
• Angiographic outcomes
• Procedural complications
• Periprocedural myocardial infarction
• Resource utilization and cost-effectiveness
• Clinical outcomes during follow-up
• Symptom improvement and angina status

Secondary procedural endpoints include quantitative flow ratio (QFR), residual stenosis by quantitative coronary angiography (QCA), device success, procedural complications, and final stent expansion measurements assessed by core laboratory analysis.

Clinical follow-up will occur at 1 month, 6 months, and 1 year after the index procedure. Follow-up assessments will include evaluation of adverse cardiovascular events, repeat revascularization, myocardial infarction, hospitalization, mortality, and angina status.

The trial also includes a parallel prospective observational registry (Def-CT-PROVE) enrolling patients with lesions identified as potentially significant by CCTA but deferred from PCI according to operator clinical judgment. This registry is intended to evaluate the natural history and clinical outcomes of deferred lesions adjudicated as hemodynamically or anatomically significant by the CCTA core laboratory analysis.

All CCTA analyses and virtual PCI planning will be performed centrally by the cardiovascular team at the Clinical Research Facility, Galway University Hospital, to ensure standardization and consistency across participating centers. The trial is designed to reflect real-world interventional practice across experienced European PCI centers while preserving operator autonomy in procedural decision-making.

The anticipated study duration for each participant is approximately 1 year. The planned sample size for the randomized CT-PROVE trial is 200 patients, with an additional prospective registry enrolling approximately 200 deferred lesions.

Inclusion Criteria:

• Adults aged 18 to 80 years

• Ability to provide written informed consent

• Patients undergoing coronary computed tomography angiography (CCTA) for suspected coronary artery disease or for diagnostic work-up of stabilized acute coronary syndrome

• Presence of at least one target coronary lesion meeting one of the following CCTA criteria:

  • Severe coronary diameter stenosis (70-99%) in one or more coronary arteries according to CAD-RADS 4A or 4B classification and at least one of the following:
  • CT-derived fractional flow reserve (CT-FFR) ≤0.80
  • At least 2 high-risk plaque characteristics, including:
  • Low attenuation plaque density <30 Hounsfield units
  • Positive remodeling index >1.1
  • Napkin-ring sign
  • Spotty calcification
  • Left main coronary artery stenosis ≥50%
  • Ostial or proximal left anterior descending artery, dominant left circumflex artery, or dominant right coronary artery stenosis ≥50% and at least one of the following:
  • CT-FFR ≤0.80
  • At least 2 high-risk plaque characteristics, including:
  • Low attenuation plaque density <30 Hounsfield units
  • Positive remodeling index >1.1
  • Napkin-ring sign
  • Spotty calcification

• Planned clinically indicated invasive coronary angiography with operator decision to proceed with PCI

Exclusion Criteria:

• Contraindication to iodinated contrast media, including severe allergy or contrast-induced nephropathy
• Poor-quality or non-diagnostic CCTA imaging
• Target lesions involving in-stent restenosis
• Chronic total occlusion target lesions
• Operator decision to treat a vessel not identified as a target vessel by the CCTA core laboratory analysis
• Pregnancy or breastfeeding
• Patients referred for coronary artery bypass graft surgery after invasive coronary angiography
• Participation in another investigational drug or drug-coated device study
• Inability to provide informed consent