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)

Fundación EPIC700 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

700

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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. * 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).

Locations (14)

Bringham and Women's Hospital

Boston, Massachusetts, United States

NOT_YET_RECRUITING

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

RECRUITING

HACKENSACK MERIDIAN HEALTH, Inc

Jersey City, New Jersey, United States

NOT_YET_RECRUITING

Columbia University Irving Medical Center/NewYork-Presbyterian Hospital

New York, New York, United States

NOT_YET_RECRUITING

Weill Medical College of Cornell University

New York, New York, United States

NOT_YET_RECRUITING

Azorg Hospital, Aalst

Aalst, Belgium

RECRUITING

Hospital Universitari Vall Hebron

Barcelona, Spain

RECRUITING

Hospital Universitario de Leon

León, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

RECRUITING

...and 4 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 12 months

Secondary Outcomes

Procedural efficiency: Procedure time

Time from first angiogram to final angiogram

Time frame: During PCI

Procedural efficiency:Radiation dose-area product

Dose-area product (DAP) recorded during PCI.

Time frame: During PCI

Procedural efficiency: Contrast volume

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

Time frame: During PCI

Procedural Efficiency: Stent Area on Immediate Post-Stent IVUS

MSA prior to any final IVUS-guided optimization.

Time frame: Perioperative/Periprocedural

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

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

Time frame: Perioperative/Periprocedural

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

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

Time frame: Perioperative/Periprocedural

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.

Time frame: Perioperative/Periprocedural

Procedural Efficiency: Relative Stent Expansion

Percentage expansion calculated as: MSA ÷ mean distal reference lumen area × 100.

Time frame: Perioperative/Periprocedural

Procedural Efficiency: Number of Calcium Fractures

Fractures identified on intermediary IVUS after calcium modification.

Time frame: Post-modification, pre-stent

Procedural Efficiency: Change in Plaque Attenuation

Change in IVUS plaque characteristics following calcium modification.Angiographic Endpoints

Time frame: Post-modification, pre-stent

Procedural Efficiency: Final Minimal Lumen Diameter

Minimum lumen diameter by quantitative coronary angiography (QCA)

Time frame: Perioperative/Periprocedural

Procedural Efficiency: Final Percent Diameter Stenosis

Percent stenosis of treated lesion after PCI, by QCA

Time frame: Perioperative/Periprocedural

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)

Time frame: Perioperative/Periprocedural

Procedural Efficiency: Angiographic Complications

According to Coronary dissection (NHLBI classification)

Time frame: Day of procedure

Procedural Efficiency: Angiographic Complications

According to Coronary perforation (Ellis classification)

Time frame: Day of procedure

Procedural Efficiency: Angiographic Complications

Slow-flow / no-reflow

Time frame: Day of procedure

Procedural Efficiency: Angiographic Complications

Side branch closure (TIMI 0-1)

Time frame: Day of procedure

Clinical & Safety Outcomes: Procedural Success

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

Time frame: Perioperative/Periprocedural

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

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

Time frame: Day 0-1

Clinical & Safety Outcomes: Stent Thrombosis

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

Time frame: Up to 12 months

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

Time frame: 12 months

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

Time frame: Baseline to 12 months

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)

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts