A Prospective, Multicenter, Randomized Controlled Trial to Investigate the Value of Coronary CT Angiography in the Understanding and Management of Coronary Calcium (The Optimal Trial)

NCT07286578 | Recruiting DMC

• 1 other identifier: EPIC46-THE OPTIMAL TRIAL
• Study Type: interventional
• Target: 700
• Locations: 3 countries
• Sites: 13

Brief Summary

The OPTIMAL randomized clinical trial has been designed to compare two imaging strategies and to test the hypothesis that a calcium modification strategy informed by coronary CT angiography (CCTA) will improve procedural efficiency and effectiveness compared with the current standard of care (IVUS-guided PCI) while achieving similar clinical outcomes in patients with hemodynamically significant calcified coronary artery disease.

Conditions

Cardiovascular Diseases; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Coronary Artery Disease

Keywords

IVUS; CT

Outcome Measures

Primary Outcomes (2)

• Demonstrate that CT-guided calcium modification results in a superior final MSA Minimal Stent Area (MSA) - Imaging Endpoint (Superiority)

  Final post-PCI minimal stent area per target lesion, measured by independent core laboratory using intravascular ultrasound (IVUS). Assesses whether CT-guided calcium modification results in superior stent expansion compared with IVUS-guided PCI.

  Perioperative/Periprocedural

• Target Vessel Failure (TVF) - Clinical Endpoint (Non-Inferiority)

  Composite of cardiac death, target-vessel myocardial infarction (TV-MI), or ischemia-driven target vessel revascularization (ID-TVR). TV-MI and ID-TVR are defined according to ARC-2 and the Fourth Universal Definition of MI.

  12 months

Secondary Outcomes (22)

• Procedural efficiency: Procedure time

  During PCI

• Procedural efficiency:Radiation dose-area product

  During PCI

• Procedural efficiency: Contrast volume

  During PCI

• Procedural Efficiency: Stent Area on Immediate Post-Stent IVUS

  Perioperative/Periprocedural

• Procedural Efficiency: Final Stent Area at Original Minimal Lumen Area (MLA)

  Perioperative/Periprocedural

Study Arms (2)

CT-guide calcium modification strategy

EXPERIMENTAL

Pre-procedural CT will be used to determine lesion characteristics.

Device: CT(Computed Tomography) guided Percutaneous Coronary Intervention

IVUS-guide calcium modification strategy

ACTIVE COMPARATOR

Pre-procedural IVUS will be used to determine lesion characteristics.

Device: IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention

Interventions

CT(Computed Tomography) guided Percutaneous Coronary Intervention DEVICE

CT will be used to determine lesion characteristics and post-procedural IVUS to confirm correct implantation of stent

CT-guide calcium modification strategy

IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention DEVICE

IVUS will be used to determine lesion characteristics and post-procedural IVUS to confirm correct implantation of stent

IVUS-guide calcium modification strategy

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must be at least 18 years of age and younger than 85 years old
• Subject must have evidence of myocardial ischemia (e.g., stable angina, silent ischemia (ischemia in the absence of chest pain or other anginal equivalents), unstable angina, or acute myocardial infarction) suitable for PCI. Patients with a clinical indication for revascularization presenting with stable coronary artery disease or stabilized acute coronary syndrome defined as follows unstable angina (Braunwald class IB, IC, IIB, IIC, IIIB, IIIC), patients with NSTEMI without high-risk features such as recurrence of chest pain, ST-segment depression\>1mm in ≥6 leads plus STsegment elevation in aVR, life-threatening arrhythmias, mechanical complications of MI, resuscitated cardiac arrest, GRACE risk score\>140.
• All target vessels must have reference vessel diameter (visually assessed by CCTA) ≥ 2.5 mm
• Subject must provide written informed consent before any study-related procedure

You may not qualify if:

• STEMI as the clinical presentation.
• Uncontrolled or recurrent ventricular tachycardia.
• Hemodynamic instability.
• Hemodialysis or peritoneal dialysis.
• Left main coronary artery stenosis \> 50%
• Atrial fibrillation, flutter, or arrhythmias during CT acquisition.
• Previous PCI in the target vessel or CABG.
• BMI ≥ 40 kg/m2
• Insufficient CT quality assessed by the Core lab.
• Comorbidity with life expectancy ≤ 2 years.
• Planned major cardiac or non-cardiac surgery within 24 months after the index procedure Note: Major surgery is any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered. Note: Minor surgery is an operation on the superficial structures of the body or a manipulative procedure that does not involve a serious risk. Planned minor surgery is not excluded.
• The subject has received a solid organ transplant that is functioning or is active on a waiting list for any solid organ transplants with expected transplantation within 24 months.
• The subject receives immunosuppressant therapy or has known immunosuppressive or severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.
• The subject has previously received or is scheduled to receive radiotherapy to a coronary artery (vascular brachytherapy) or the chest/mediastinum.
• Subject has a platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3.

Sponsors & Collaborators

• Fundación EPIC: lead

Study Sites (13)

Bringham and Women's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

NOT YET RECRUITING

HACKENSACK MERIDIAN HEALTH, Inc

Jersey City, New Jersey, 08837, United States

NOT YET RECRUITING

Columbia University Irving Medical Center/NewYork-Presbyterian Hospital

New York, New York, 10032, United States

NOT YET RECRUITING

Weill Medical College of Cornell University

New York, New York, 14853, United States

NOT YET RECRUITING

Hospital Universitari Vall Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario de Leon

León, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

NOT YET RECRUITING

St Bartholomew's Hospital (Barts Health NHS Trust)

London, United Kingdom

NOT YET RECRUITING

St George's University Hospitals NHS Foundations Trust

London, United Kingdom

NOT YET RECRUITING

Newcastle Hospitals NHS Foundations Trust

Newcastle, United Kingdom

NOT YET RECRUITING

John Radcliffe Hospital, Oxford

Oxford, United Kingdom

NOT YET RECRUITING

Related Publications (5)

• Collet C, Sonck J, Vandeloo B, Mizukami T, Roosens B, Lochy S, Argacha JF, Schoors D, Colaiori I, Di Gioia G, Kodeboina M, Suzuki H, Van 't Veer M, Bartunek J, Barbato E, Cosyns B, De Bruyne B. Measurement of Hyperemic Pullback Pressure Gradients to Characterize Patterns of Coronary Atherosclerosis. J Am Coll Cardiol. 2019 Oct 8;74(14):1772-1784. doi: 10.1016/j.jacc.2019.07.072.

  PMID: 31582137 BACKGROUND

• Tajima A, Bouisset F, Ohashi H, Sakai K, Mizukami T, Rizzini ML, Gallo D, Chiastra C, Morbiducci U, Ali ZA, Spratt JC, Ando H, Amano T, Kitslaar P, Wilgenhof A, Sonck J, De Bruyne B, Collet C. Advanced CT Imaging for the Assessment of Calcific Coronary Artery Disease and PCI Planning. J Soc Cardiovasc Angiogr Interv. 2024 Mar 26;3(3Part B):101299. doi: 10.1016/j.jscai.2024.101299. eCollection 2024 Mar.

  PMID: 39131223 BACKGROUND

• Monizzi G, Sonck J, Nagumo S, Buytaert D, Van Hoe L, Grancini L, Bartorelli AL, Vanhoenacker P, Simons P, Bladt O, Wyffels E, De Bruyne B, Andreini D, Collet C. Quantification of calcium burden by coronary CT angiography compared to optical coherence tomography. Int J Cardiovasc Imaging. 2020 Dec;36(12):2393-2402. doi: 10.1007/s10554-020-01839-z. Epub 2020 Nov 17.

  PMID: 33205340 BACKGROUND

• Sonck J, Nagumo S, Norgaard BL, Otake H, Ko B, Zhang J, Mizukami T, Maeng M, Andreini D, Takahashi Y, Jensen JM, Ihdayhid A, Heggermont W, Barbato E, Mileva N, Munhoz D, Bartunek J, Updegrove A, Collinsworth A, Penicka M, Van Hoe L, Leipsic J, Koo BK, De Bruyne B, Collet C. Clinical Validation of a Virtual Planner for Coronary Interventions Based on Coronary CT Angiography. JACC Cardiovasc Imaging. 2022 Jul;15(7):1242-1255. doi: 10.1016/j.jcmg.2022.02.003. Epub 2022 Apr 13.

  PMID: 35798401 BACKGROUND

• Collet C, Collison D, Mizukami T, McCartney P, Sonck J, Ford T, Munhoz D, Berry C, De Bruyne B, Oldroyd K. Differential Improvement in Angina and Health-Related Quality of Life After PCI in Focal and Diffuse Coronary Artery Disease. JACC Cardiovasc Interv. 2022 Dec 26;15(24):2506-2518. doi: 10.1016/j.jcin.2022.09.048. Epub 2022 Nov 30.

  PMID: 36543445 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease

Central Study Contacts

CAROLINA FOCELLA

CONTACT

001 917 753 6695; cfocella@crf.org

CARLOS COLLET, MD,PhD

CONTACT

001 917 753 6695; carloscollet@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: December 16, 2025
• Study Start: December 22, 2025
• Primary Completion (Estimated): December 15, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

ES (3); GB (5); US (5)