The OPTIMAL Randomized Controlled Trial (OPTIMAL)

OPtimizaTIon of Left MAin PCI With IntravascuLar Ultrasound. The OPTIMAL Randomized Controlled Trial

The OPTIMAL study is a randomized, controlled, multicentre, international study. A total of 800 patients will be randomized in a 1:1 fashion to Intravascular Ultrasound (IVUS)-guided PCI versus qualitative angio(QCA)-guided Percutaneous Coronary Intervention (PCI). Patients will be consented prior to the PCI procedure and then followed up to 2 years after the index procedure for the last enrolled patient. Patients will be followed-up at 1 month (telephone contact), 12 months (outpatient clinic visit or telephone call) and yearly after (outpatient clinic visit or telephone call).

Study Overview

• Status: Completed
• Conditions: Left Main Coronary Artery Stenosis
• Intervention / Treatment: Device: IVUS guided Percutaneous Coronary Intervention; Device: Qualitative or quantitative angiography will guide percutaneous coronary intervention

• Study Type: Interventional
• Enrollment (Actual): 806
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy
    • Asst Papa Giovanni XXIII
  • Ferrara, Italy
    • A.O.U. di Ferrara
  • Florence, Italy
    • Interventistica Cardiologica Strutturale
  • Milan, Italy
    • ASST Niguarda
  • Milan, Italy
    • Policlinco San Donato
  • Milan, Italy
    • Sant'Ambrogio Clinical Institute
  • Rome, Italy
    • Policlinico Umberto I
  • Verona, Italy
    • AOUI Verona
• Spain
  • A Coruña, Spain
    • Hospital Universitario de A Coruña
  • Barcelona, Spain
    • Hospital de Bellvitge
  • Barcelona, Spain
    • Hospital Vall D´Hebron
  • Córdoba, Spain
    • Hospital Reina Sofia
  • Gijón, Spain
    • Hospital de Cabueñes
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Murcia, Spain
    • Hospital Clinico Universiatrio V. Arrixaca
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecilla
  • Vigo, Spain
    • Hospital Alvaro Cunqueiro
  • Zaragoza, Spain
    • Hospital Clinico Lozano Blesa
• United Kingdom
  • Belfast, United Kingdom
    • Royal Victoria Hospital
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • Brighton, United Kingdom
    • Royal Sussex Country Hospital
  • Bristol, United Kingdom
    • Bristol Royal Infirmary
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • Clydebank, United Kingdom
    • Golden Jubilee National Hospital
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • London, United Kingdom
    • St Bartholomew's Hospital
  • Newcastle upon Tyne, United Kingdom
    • The Freeman Hospital
  • Oxford, United Kingdom
    • John Radcliffe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient must be ≥ 18 years of age;
2. De novo lesion in an unprotected left main coronary artery (ULMCA; ostial, shaft or distal) OR ostial left anterior descending artery (LAD) or ostial circumflex (LCX), both compatible with one Medina class of LM disease; or ostial intermediate branch disease;
3. PCI is considered appropriate and feasible by the treating interventionalist;
4. Silent ischemia, stable angina, unstable angina, or non-ST segment elevation MI;
5. Able to understand and provide informed consent and comply with all study procedures, including follow-up for at least 2 years.

Note: A patient with a prior CABG with no patent bypass on the left main coronary artery (LMCA) can be included.

Exclusion Criteria:

1. Patient is a woman who is pregnant or nursing;
2. Female patient of childbearing potential, i.e. who are not surgically sterile or post-menopausal (defined as no menses for 2 years without an alternative cause);
3. IVUS is strictly required for pre-PCI lesion severity assessment
4. ST-elevation myocardial infarction, cardiogenic shock;
5. Previous history of CABG with patent graft to the LAD and/or patent graft to the LCX;
6. Prior PCI of the LM, ostial LAD or ostial LCX at any time prior to enrollment;
7. Prior PCI of any other (i.e. non-LM, non-ostial-LAD and non-ostial-LCX) coronary artery lesions within 30 days prior to enrollment;
8. Patients unable to tolerate, obtain or comply with dual antiplatelet therapy for at least 6 months in stable patients and 1 year in ACS patients;
9. Known contraindication or hypersensitivity to everolimus, platinum-chromium, or to anticoagulants.
10. Patients requiring additional surgery (cardiac or non-cardiac) within 3 months post-enrollment;
11. Non-cardiac co-morbidities with a life expectancy less than 2 years;
12. Currently participating in another trial that is not yet at its primary endpoint. The patient is not allowed to participate in another investigational device or drug study for at least 12 months after enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IVUS guided PCI; Pre-procedural IVUS will be used to determine lesion characteristics and post-procedural IVUS to confirm correct implantation of stent.	Device: IVUS guided Percutaneous Coronary Intervention; Pre-procedural IVUS will be used to determine lesion characteristics and post-procedural IVUS to confirm correct implantation of stent.
Active Comparator: Angiography-guided PCI; Qualitative or quantitative angiography will be used to determine lesion characteristics	Device: Qualitative or quantitative angiography will guide percutaneous coronary intervention; Qualitative or quantitative angiography will be used to determine lesion characteristics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-oriented Composite Endpoint (POCE)	Patient-oriented Composite Endpoint (PoCE): composite of all-cause death, any stroke, any myocardial infarction (MI)*, any clinically indicated revascularization at longest follow-up.	2-5 years follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device-oriented Composite Endpoint (DoCE)	Device-oriented Composite Endpoint (DoCE) defined as the composite of: Cardiovascular death, target vessel MI, clinically indicated repeat revascularization of the target lesion at longest follow-up	2-5 years follow up
Vessel-oriented Composite Endpoint (VoCE)	Vessel-oriented Composite Endpoint (VoCE) defined as the composite of: left main related cardiac death, target vessel MI, clinically indicated -repeat revascularization of the left main vessels at longest follow-up.	2-5 years follow up
Patient-oriented Composite Endpoint (POCE)	Patient-oriented Composite Endpoint (PoCE): composite of all-cause death, any stroke, any myocardial infarction (MI)*, any clinically indicated revascularization at 2 years follow-up.	2 year follow up
All individual components of PoCE at all time points.	All individual components of PoCE at all time points.	2-5 years follow-up
All individual components of DoCE at all time points.	All individual components of DoCE at all time points.	2-5 years follow-up
Definite and probable stent thrombosis	Definite and probable stent thrombosis according to ARC definition	2-5 years follow-up
Hospitalization for heart failure	Investigator reported hospitalization for heart failure	2-5 years follow-up

Collaborators and Investigators

• Sponsor: ECRI bv
• Collaborators: Boston Scientific Corporation; Philips Healthcare; Cardialysis B.V.
• Investigators: Principal Investigator: Adrian Banning, Prof, Oxford University Hospitals NHS Trust; Principal Investigator: Luca Testa, Dr., Policlinco San Donato

Publications and helpful links

General Publications

• De Maria GL, Testa L, de la Torre Hernandez JM, Terentes-Printzios D, Emfietzoglou M, Scarsini R, Bedogni F, Spitzer E, Banning A. A multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease: Study protocol for OPTIMAL trial. PLoS One. 2022 Jan 7;17(1):e0260770. doi: 10.1371/journal.pone.0260770. eCollection 2022.
• Testa L, De la Torre Hernandez JM, De Maria GL, Jones DA, Pinon-Esteban P, Campo G, Garcia Del Blanco B, Pan M, Garcia-Camarero T, Sardella G, O'Kane P, Greenwood JP, Ribichini FL, Pescetelli I, Ielasi A, Lozano I, Cockburn J, Oreglia JA, Zaman AG, Bedogni F, Lindeboom W, Tijssen JGP, Spitzer E, Banning AP; OPTIMAL Investigators. IVUS-Guided versus Angiography-Guided PCI in Unprotected Left Main Coronary Disease. N Engl J Med. 2026 Mar 30. doi: 10.1056/NEJMoa2600440. Online ahead of print.

Helpful Links

• Rationale and Design of the OPTIMAL Trial

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Actual): July 31, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: September 30, 2019
• First Posted (Actual): October 1, 2019

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: PCI; IVUS; Left Main; QCA; Treatment Strategy
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Coronary Stenosis
• Other Study ID Numbers: ECRI-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes