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Cardiovascular DiseasesNCT07286578

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)

A study testing CT(Computed Tomography) guided Percutaneous Coronary Intervention and IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention in people with Cardiovascular Diseases and Myocardial Ischemia, run by Fundación EPIC at 14 sites in 4 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
CT(Computed Tomography) guided Percutaneous Coronary Intervention and IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
700 participants
Where
14 sitesin 4 countries
Study dates
22 Dec 2025to 1 Jan 2030
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 21Show fewer
  • 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.
  • The subject has a documented or suspected hepatic disorder as defined as cirrhosis or Child-Pugh ≥ Class B.
  • The subject has a history of bleeding diathesis or coagulopathy or has had a significant gastro-intestinal or significant urinary bleed within the past six months. The subject has had a cerebrovascular accident or transient ischemic neurological attack (TIA) within the past six months, or any prior intracranial bleed, or any permanent neurologic defect, or any known intracranial pathology (e.g., aneurysm, arteriovenous malformation, etc. The subject has a life expectancy <2 years for any non-cardiac cause.
  • Subject is currently participating in another investigational drug or device clinical study.
  • Pregnant or nursing subjects and those who plan pregnancy in the period up to 2 years following index procedure. Female subjects of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test.
  • Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
  • Unable to provide written informed consent (IC).

Trial locations and contacts

14 sites in 4 countries. Contact the study team or a site near you to ask about taking part.

CAROLINA FOCELLA contact

001 917 753 6695

cfocella@crf.org

CARLOS COLLET, MD,PhD contact

001 917 753 6695

carloscollet@gmail.com

14 sites in 4 countries

United States5 sites, 5 recruiting

  • Bringham and Women's Hospital

    Boston, Massachusetts, 02115

    Not yet recruiting

  • HACKENSACK MERIDIAN HEALTH, Inc

    Jersey City, New Jersey, 08837

    Not yet recruiting

  • Minneapolis Heart Institute

    Minneapolis, Minnesota, 55407

    Recruiting

  • Columbia University Irving Medical Center/NewYork-Presbyterian Hospital

    New York, New York, 10032

    Recruiting

  • Weill Medical College of Cornell University

    New York, New York, 14853

    Not yet recruiting

Other trials in United States

United Kingdom5 sites, 5 recruiting

  • University Hospitals of Leicester NHS Trust

    Leicester

    Recruiting

  • St Bartholomew's Hospital (Barts Health NHS Trust)

    London

    Recruiting

  • St George's University Hospitals NHS Foundations Trust

    London

    James Spratt, MD, PhD

    Recruiting

  • Newcastle Hospitals NHS Foundations Trust

    Newcastle

    Not yet recruiting

  • John Radcliffe Hospital, Oxford

    Oxford

    Not yet recruiting

Other trials in United Kingdom

Spain3 sites, 3 recruiting

  • Hospital Universitari Vall Hebron

    Barcelona, 08035

    Recruiting

  • Hospital Universitario de Leon

    León

    Recruiting

  • Hospital Universitario La Paz

    Madrid, 28046

    Recruiting

Other trials in Spain

Belgium1 site, 1 recruiting

  • Azorg Hospital, Aalst

    Aalst, 9300

    Recruiting

Other trials in Belgium

About this study

Official title: A Prospective, Multicenter, Randomized Controlled Trial to Investigate the Value of Coronary CT Angiography in the Understanding and Management of Coronary Calcium

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.

Read the detailed description

The OPTIMAL Trial is a prospective, multicenter, randomized controlled study evaluating whether a coronary CT angiography (CCTA)-guided calcium modification strategy can improve the treatment of patients with hemodynamically significant, calcified coronary artery disease undergoing percutaneous coronary intervention (PCI).

Seven hundred patients with flow-limiting stenosis (FFRCT ≤0.80) and moderate-to-severe calcification on CCTA will be randomized 1:1 to either CCTA-guided or intravascular ultrasound (IVUS)-guided calcium modification. The study includes two co-primary endpoints: (1) superiority in final minimal stent area assessed by IVUS, and (2) non-inferiority in 12-month target vessel failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven revascularization).

CCTA-guided strategy uses advanced calcium characterization to inform pre-procedural planning and selection of plaque modification techniques. IVUS-guided strategy follows contemporary intravascular imaging-based criteria for plaque preparation and PCI optimization.

The trial aims to determine whether leveraging non-invasive CT-based calcium assessment can enhance procedural efficiency and stent results while maintaining clinical safety comparable to IVUS-guided PCI.

Being tested
CT(Computed Tomography) guided Percutaneous Coronary Intervention, IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention
Keywords
IVUS, CT
Medical subject headings
Cardiovascular Diseases, Myocardial Ischemia, Heart Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CT(Computed Tomography) guided Percutaneous Coronary InterventionDevice

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

  • IVUS (Intravascular Ultrasound) guided Percutaneous Coronary InterventionDevice

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

Study groups in NCT07286578
Study groupRoleWhat they receive
CT-guide calcium modification strategyExperimentalPre-procedural CT will be used to determine lesion characteristics.
Receives: Device: CT(Computed Tomography) guided Percutaneous Coronary Intervention
IVUS-guide calcium modification strategyActive comparatorPre-procedural IVUS will be used to determine lesion characteristics.
Receives: Device: IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Perioperative/Periprocedural

  2. 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.

    Measured: 12 months

Secondary outcomes (22)

  1. Procedural efficiency: Procedure time

    Time from first angiogram to final angiogram

    Measured: During PCI

  2. Procedural efficiency:Radiation dose-area product

    Dose-area product (DAP) recorded during PCI.

    Measured: During PCI

  3. Procedural efficiency: Contrast volume

    Total contrast volume (mL) used during PCI.IVUS-Derived Mechanistic Endpoints (Core Lab)

    Measured: During PCI

  4. Procedural Efficiency: Stent Area on Immediate Post-Stent IVUS

    MSA prior to any final IVUS-guided optimization.

    Measured: Perioperative/Periprocedural

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

    Stent area at the co-registered site of the baseline MLA.

    Measured: Perioperative/Periprocedural

  6. Procedural Efficiency: Final Stent Area at Site of Maximum Calcium Arc

    Stent area measured at the co-registered IVUS site with maximal calcium arc

    Measured: Perioperative/Periprocedural

  7. Procedural Efficiency: Final Stent Area at Site of Maximum Calcium Density

    Stent area measured at the co-registered CT-identified region of greatest Hounsfield Unit (HU) calcium density.

    Measured: Perioperative/Periprocedural

  8. Procedural Efficiency: Relative Stent Expansion

    Percentage expansion calculated as:

    MSA ÷ mean distal reference lumen area × 100.

    Measured: Perioperative/Periprocedural

  9. Procedural Efficiency: Number of Calcium Fractures

    Fractures identified on intermediary IVUS after calcium modification.

    Measured: Post-modification, pre-stent

  10. Procedural Efficiency: Change in Plaque Attenuation

    Change in IVUS plaque characteristics following calcium modification.Angiographic Endpoints

    Measured: Post-modification, pre-stent

  11. Procedural Efficiency: Final Minimal Lumen Diameter

    Minimum lumen diameter by quantitative coronary angiography (QCA)

    Measured: Perioperative/Periprocedural

  12. Procedural Efficiency: Final Percent Diameter Stenosis

    Percent stenosis of treated lesion after PCI, by QCA

    Measured: Perioperative/Periprocedural

  13. Procedural Efficiency: Final TIMI Flow Grade

    Target vessel flow graded 0-3 based on TIMI criteria. Thrombolysis In Myocardial Infarction (TIMI) Flow Grade is a 0-3 angiographic scale used during coronary angiography to describe how well blood is flowing through a coronary artery.TIMI 0 No perfusion, TIMI 1 Penetration without perfusion, TIMI 2 Partial perfusion TIMI 3 Complete perfusion (normal flow)

    Measured: Perioperative/Periprocedural

  14. Procedural Efficiency: Angiographic Complications

    According to Coronary dissection (NHLBI classification)

    Measured: Day of procedure

  15. Procedural Efficiency: Angiographic Complications

    According to Coronary perforation (Ellis classification)

    Measured: Day of procedure

  16. Procedural Efficiency: Angiographic Complications

    Slow-flow / no-reflow

    Measured: Day of procedure

  17. Procedural Efficiency: Angiographic Complications

    Side branch closure (TIMI 0-1)

    Measured: Day of procedure

  18. Clinical & Safety Outcomes: Procedural Success

    Final stenosis <30%, TIMI 3 flow, no angiographic complications, and no in-hospital major adverse cardiac events (MACE).

    Measured: Perioperative/Periprocedural

  19. Clinical & Safety Outcomes: Periprocedural Myocardial Infarction (Type 4a MI)

    Defined by ARC-2 and 4th Universal Definition of MI (troponin criteria + evidence of ischemia).

    Measured: Day 0-1

  20. Clinical & Safety Outcomes: Stent Thrombosis

    Definite or probable stent thrombosis according to ARC-2 definitions.

    Measured: Up to 12 months

  21. Patient-Reported Outcomes: Residual Angina (SAQ-7 Angina Frequency)

    Residual angina defined as SAQ-7 Angina Frequency score <100. Angina frequency represent how often a patient has had angina (chest pain/discomfort) over a recent recall period. Reported as a 0 to 100 scale: 100 = no angina; 0 = angina occurring very frequently

    Measured: 12 months

  22. Patient-Reported Outcomes: Change in Angina (SAQ-7)

    Change in angina frequency domain score; positive values indicate improvement. Angina frequency represent how often a patient has had angina (chest pain/discomfort) over a recent recall period. Reported as a 0 to 100 scale: 100 = no angina; 0 = angina occurring very frequently

    Measured: Baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2025
  2. Study start22 Dec 2025
  3. Primary completion15 Dec 2029 (estimated)
  4. Study completion1 Jan 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
700 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07286578
Sponsor's protocol ID
EPIC46-THE OPTIMAL TRIAL
Status last verified
Oct 2026
First submitted
28 Nov 2025
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 31582137

  • 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.

    PubMed 39131223

  • 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.

    PubMed 33205340

  • 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.

    PubMed 35798401

  • 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.

    PubMed 36543445

Questions about this trial

What is this clinical trial studying?

A study testing CT(Computed Tomography) guided Percutaneous Coronary Intervention and IVUS (Intravascular Ultrasound) guided Percutaneous Coronary Intervention in people with Cardiovascular Diseases and Myocardial Ischemia, run by Fundación EPIC at 14 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, United Kingdom, Spain, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact CAROLINA FOCELLA (001 917 753 6695, cfocella@crf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Demonstrate that CT-guided calcium modification results in a superior final MSA Minimal Stent Area (MSA) - Imaging Endpoint (Superiority) (time frame: Perioperative/Periprocedural). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07286578, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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