Ultrathin-strut Biodegradable Polymer Sirolimus-eluting Stents With P2Y12 Inhibitor-based Single Antiplatelet Therapy vs. Conventional DAPT for Unprotected Left Main Coronary Artery Disease (ULTIMATE-LM)

NCT05650411 | Recruiting DMC

• 1 other identifier: 2022-1204
• Study Type: interventional
• Target: 828
• Locations: 1 country
• Sites: 1

Brief Summary

The management of patients with unprotected left main coronary artery (LMCA) disease undergoing percutaneous coronary intervention (PCI) in contemporary interventional cardiology practice remains matter of intense debate. Particularly, the combination of the optimal drug-eluting stent (DES) selection and antiplatelet regimen for patients who require LMCA PCI remains undetermined. Newer-generation drug-eluting stents with ultrathin-strut metallic platforms have been shown to reduce the risk of target lesion failure compared with thicker-strut drug-eluting stents among all-comer patients undergoing PCI, a difference mainly driven by a lower risk of ischemia-driven target lesion revascularization. In the TALENT prospective, single-blind, multicenter, randomized controlled trial that included 1'435 all-comer patients undergoing PCI, the Supraflex ultrathin-strut biodegradable polymer sirolimus-eluting stent was found non-inferior to the Xience® thin-strut permanent polymer everolimus-eluting stent (Abbott Vascular, USA) with regards to the device-oriented composite clinical endpoint (DoCE), a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization, at 12 months of follow-up. However, the TALENT trial included only 31 (1.5%) lesions located in the left main coronary artery. In the COMPARE 60/80 HBR investigator-initiated, multicenter, prospective randomized trial which included a total of 732 patients at high-bleeding risk undergoing PCI with the Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent or the Ultimaster Tansei (Terumo Corp., Tokyo, Japan), the rates of the primary endpoint of the net adverse clinical endpoint, defined as a composite of cardiac death, myocardial infarction, target vessel revascularization, stroke, or BARC 3 or 5 major bleeding events at 12 months were similar in the Supraflex Cruz and the Ultimaster Tansei groups, meeting the prespecified criterion for non-inferiority of the Supraflex Cruz DES compared to the Ultimaster Tansei DES. The safety and efficacy of the Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent combined with potent P2Y12 inhibitor aspirin-free SAPT among all-comer patients undergoing PCI for complex coronary lesions, such as patients with LMCA stenosis, have however not been investigated to date. Recent evidence from a large-scale meta-analysis of several randomized clinical trials including \>32'000 patients indicated that 1-3 months of DAPT followed by P2Y12 inhibitor single antiplatelet therapy (SAPT) after second-generation DES implantation was associated with lower risk for major bleeding and similar risk for adverse ischemic outcomes compared with conventional DAPT. These findings suggest that P2Y12 inhibitor SAPT following a short DAPT course (1-3 months) may represent a valuable treatment option for patients undergoing PCI with newer-generation DES compared to standard conventional 12 months DAPT, but this strategy has never been investigated in dedicated randomized clinical trials focused on patients at highest-risk for ischaemic events, such as patients undergoing LMCA PCI. The ULTIMATE-LM randomized trial aims at filling this current gap of knowledge, which may have large impact on clinical practice and international guidelines. ULTIMATE-LM will be the first randomized clinical trial to investigate the safety and efficacy of a novel ultrathin-strut biodegradable polymer drug-eluting stent (Supraflex Cruz, Sahajanand Medical Technologies Ltd., Surat, India)) combined with P2Y12 inhibitor-based single antiplatelet therapy among patients undergoing PCI for LMCA disease.

Conditions

Left Main Coronary Artery Stenosis

Keywords

P2Y12 inhibitor-based single antiplatelet therapy; Dual antiplatelet therapy; Left main coronary artery disease; Percutaneous coronary intervention; Ultrathin-strut; Drug-eluting stent

Outcome Measures

Primary Outcomes (1)

• Patient-oriented composite endpoint (POCE)

  Composite of all-cause death, any non-fatal myocardial infarction, or any revascularization (PCI, or CABG)

  2 years

Secondary Outcomes (11)

• Net adverse clinical and major adverse cardiac (NACE)

  2 years

• Device-oriented composite endpoint (DOCE)

  2 years

• All-cause death

  2 years

• Any non-fatal myocardial infarction

  2 years

• Any revascularization

  2 years

Study Arms (2)

P2Y12 inhibitor-based single antiplatelet therapy after a short DAPT strategy arm

EXPERIMENTAL

Successful LMCA PCI with ≥1 Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India). P2Y12 inhibitor SAPT with any of the commercially available oral P2Y12 inhibitors (ticagrelor, or prasugrel 10 mg) after a short DAPT course during 2 years after the index LMCA procedure. At the discretion of the investigator, aspirin will be discontinued after LMCA PCI, or continued during the hospital stay. In all cases, aspirin will be discontinued at latest at hospital discharge.

Device: LMCA PCI with Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India).; Drug: P2Y12 inhibitor-based SAPT after short DAPT

Conventional DAPT strategy arm

ACTIVE COMPARATOR

Successful LMCA PCI with ≥1 Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India). DAPT combining aspirin and any of the commercially available oral P2Y12 receptor inhibitors (clopidogrel, ticagrelor, or prasugrel) during 6 or 12 months followed by aspirin-based SAPT. In patients with index ACS presentation and who have tolerated DAPT for 12 months without bleeding complications, a prolonged DAPT course with aspirin and ticagrelor 60 mg bd (clopidogrel or prasugrel allowed, if patient not eligible for treatment with ticagrelor) beyond 12 months may be considered in those patients with high thrombotic risk and without an increased risk for major or life-threatening bleeding, and those with moderately elevated thrombotic risk.

Device: LMCA PCI with Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India).; Drug: Conventional DAPT

Interventions

P2Y12 inhibitor-based SAPT after short DAPT DRUG

Potent P2Y12 inhibitor-based SAPT (ticagrelor 90 mg bd, or prasugrel 5 or 10 mg od, at the discretion of the investigator) during 2 years. Aspirin stopped after LMCA or at latest at hospital discharge.

P2Y12 inhibitor-based single antiplatelet therapy after a short DAPT strategy arm

Conventional DAPT DRUG

6 to 12 months of DAPT combining aspirin (≥75 mg od) and a P2Y12 inhibitor (clopidogrel 75 mg od, ticagrelor 90 mg bd, prasugrel 5 or 10 mg od at the discretion of the investigator) followed by aspirin SAPT.

Conventional DAPT strategy arm

LMCA PCI with Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India). DEVICE

Successful LMCA PCI with ≥1 Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India).

Conventional DAPT strategy arm; P2Y12 inhibitor-based single antiplatelet therapy after a short DAPT strategy arm

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Patient with chronic or acute coronary syndrome (unstable angina, or non-ST-elevation acute coronary syndrome).
• Subject with significant unprotected (ostial, mid-shaft, or distal) LMCA stenosis who underwent successful LMCA PCI with ≥1 Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India) according to current ESC guidelines on myocardial revascularization and/or local Heart Team decision.
• Subject willing to participate and able to understand, read and sign the informed consent document before the planned procedure.

You may not qualify if:

• Contraindications to PCI and/or DES implantation.
• Inability to adhere to DAPT for at least 6 months.
• Patient already on DAPT.
• Patients on oral anticoagulation.
• Previous coronary artery bypass surgery.
• LMCA in-stent restenosis or stent thrombosis.
• Recent ST-elevation myocardial infarction \<5 days prior to randomization.
• Cardiogenic shock/hemodynamic instability at the time of intervention and/or need for mechanical/pharmacologic hemodynamic support.
• Participation or planned participation in another clinical trial, except for observational registries.
• Life expectancy \<1 year.
• Pregnancy.

Sponsors & Collaborators

• University of Bern: collaborator
• IGLESIAS Juan Fernando: lead

Study Sites (1)

Zurich University Hospital

Zurich, Canton of Zurich, Switzerland

RECRUITING

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Juan F. Iglesias, MD

  Geneva University Hospitals, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maëlle Achard, RN

CONTACT

+41795533553; maelle.achard@hcuge.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 4, 2022
• First Posted: December 14, 2022
• Study Start: April 26, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2032
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After publication of the study primary and secondary endpoints.

Locations

CH (1)