Intravascular Ultrasound- and Angiography-Derived Fractional Flow Reserve-Guided Drug-Coated Balloon for Large Coronary Artery De Novo Lesions

Summary

Trial name Intravascular Ultrasound- and Angiography-Derived Fractional Flow Reserve-Guided Drug-Coated Balloon for Large Coronary Artery De Novo Lesions Objectives To compare the safety and efficacy of Drug-Coated Balloons (DCB) versus Drug-Eluting Stents (DES) in large de novo coronary lesions guided by intravascular ultrasound (IVUS) and Angiography-derived fractional flow reserve (AngioFFR).

Study design Investigator-initiated, open-label, multicenter, non-inferiority randomized controlled trial Patient enrollment 2,492 patients enrolled in China and Republic of Korea. Duration Anticipated recruitment is 2 years. Follow-up will be performed at 1, 3, 6, 12, 36, and 60 months.

Inclusion Criteria

1. Patients must require PCI based on clinical condition (angiographic stenosis ≥ 75% or angiographic stenosis ≥ 50% with AngioFFR≤0.80) and have signed the informed consent form.
2. Coronary angiography shows a single non-left main lesion, with a reference vessel diameter between 2.75mm and 4.00mm, and an estimated lesion length \< 40mm.
3. Following adequate intraoperative lesion preparation, the following must be met: IVUS shows MLA≥ 4.0mm² and/or AnioFFR \> 0.80.
4. Absence of flow-limiting dissection or hematoma (angiographic Type A or B dissection; IVUS dissection not involving the media) and TIMI flow grade 3
5. Patients must be able to be followed up for more than 1 year and be willing to cooperate with the trial follow-up requirements.

Exclusion Criteria

1. Patients are younger than 19 or older than 80 years of age.
2. High-Risk Clinical/Anatomical Factors: Cardiogenic shock, left main disease, severely tortuous lesions, complex bifurcation lesions, severe calcification, total occlusion of the target vessel, or bypass grafts.
3. Recent major surgery (within 1 month pre-procedure) or clear gastrointestinal bleeding events.
4. Known allergy or contraindication to heparin, aspirin, clopidogrel, prasugrel, ticagrelor, or contrast media (patients with clear contrast allergies such as rash may be included if controlled beforehand with effective medication like glucocorticoids or diphenhydramine).
5. Women who are currently pregnant or breastfeeding.
6. Non-cardiac comorbidities indicating an expected life expectancy of less than 1 year.
7. Any other factors that may affect follow-up or participation in other clinical studies.

Patient follow-up Clinical follow-up will perform 1, 6, 12, 36 and 60 months after the procedure by telephone contacts or office visits.

Primary endpoint

The study employs a hierarchical testing (sequential testing) approach, following the logical order below:

1.12-Month Net Adverse Clinical Events (NACE): Defined as a composite endpoint consisting of all-cause death, stroke, myocardial infarction (MI), ischemia-driven revascularization, and bleeding (BARC 3 or 5).

2.Ischemic Endpoint - Major Adverse Cardiac and Cerebrovascular Events (MACCE): Defined as the composite of death, MI, ischemia-driven revascularization, and ischemic stroke.

3.Bleeding Endpoint: Defined as 12-month major bleeding or clinically relevant non-major bleeding, categorized as BARC 2, 3, or 5.

Secondary endpoint

1. Target Vessel Failure (TVF): A composite of cardiac death, target vessel MI, or target vessel revascularization.
2. NACE, major bleeding or clinically relevant non-major bleeding, and MACCE at 36 and 60 months.
3. All-cause death and cardiac death.
4. MI, spontaneous MI, peri-procedural MI, and target vessel MI.
5. Any revascularization of the target vessel/target lesion.
6. Any revascularization of a non-target vessel/ non-target lesion.
7. Any revascularization (ischemia-driven or all-cause).
8. Stent Thrombosis: Classified as definite, probable, or possible.
9. Stroke: Including both ischemic and hemorrhagic stroke.
10. Bleeding Events: BARC 3 or 5 bleeding, and BARC 2 bleeding.
11. Evaluation of cost-effectiveness.

Conditions

• Coronary Artery Disease

Interventions

DEVICE

DCB in large de novo coronary lesions guided by IVUS and AngioFFR

Visual reference vessel diameter of 2.75 mm to 4 mm. Lesion pre-treatment: Adequate pre-treatment of the lesion was performed (including use of semi-compliant / non-compliant balloons or specialty balloons). Imaging and functional assessment: After pre-treatment, the lesion met the following physiological and anatomical requirements: IVUS: MLA ≥ 4.0 mm²; And/or AngioFFR \> 0.80. No flow-limiting dissection, defined as: Coronary angiography: Only type A or type B dissection present; IVUS: Dissection not involving the vascular media; Coronary flow: TIMI flow grade 3 maintained. * Patients receive DAPT for 1 month. * After 1 month, therapy is switched to SAPT, with Clopidogrel as the preferred agent. * Oral Anticoagulants: If the patient is concurrently taking oral anticoagulants, they will receive SAPT plus anticoagulation for 1 month, followed by anticoagulation alone.

DEVICE

DES in large de novo coronary lesions guided by IVUS and AngioFFR

Visual reference vessel diameter of 2.75 mm to 4 mm. Lesion pre-treatment: Adequate pre-treatment of the lesion was performed (including use of semi-compliant / non-compliant balloons or specialty balloons). Imaging and functional assessment: After pre-treatment, the lesion met the following physiological and anatomical requirements: IVUS: MLA ≥ 4.0 mm²; And/or AngioFFR \> 0.80. No flow-limiting dissection, defined as: Coronary angiography: Only type A or type B dissection present; IVUS: Dissection not involving the vascular media; Coronary flow: TIMI flow grade 3 maintained. * Patients receive DAPT for at least 6 months following DES implantation. * Subsequent antiplatelet regimens are determined by the operator's discretion. * Oral Anticoagulants: If the patient is concurrently taking oral anticoagulants, they will receive DAPT plus anticoagulation for 1 month, followed by SAPT plus anticoagulation. DCB or DES Used in PCI.

Sponsors & Collaborators

• Ulsan University Hospital

  collaborator OTHER

• Shanghai Zhongshan Hospital

  collaborator OTHER

• First Affiliated Hospital of Wenzhou Medical University

  collaborator OTHER

• The First People's Hospital of Huzhou

  collaborator OTHER

• Huzhou Central Hospital

  collaborator OTHER

• First Affiliated Hospital of Ningbo University

  collaborator NETWORK

• Ningbo Medical Center Lihuili Hospital

  collaborator OTHER_GOV

• Yiwu Central Hospital

  collaborator OTHER

• People's Hospital of Quzhou

  collaborator OTHER

• Lishui Country People's Hospital

  collaborator OTHER

• First Affiliated Hospital of Guangxi Medical University

  collaborator OTHER

• First People's Hospital of Yulin

  collaborator OTHER

• Longyan First Hospital, Affiliated to Fujian Medical University

  collaborator UNKNOWN

• Fourth Affiliated Hospital of Xinjiang Medical University

  collaborator OTHER

• Shangrao People's Hospital

  collaborator UNKNOWN

• Fuyang people's hospital

  collaborator OTHER

• First People's Hospital of Xianyang

  collaborator OTHER

• The First People's Hospital of Yunnan

  collaborator OTHER

• Second Affiliated Hospital, School of Medicine, Zhejiang University

  lead OTHER

Principal Investigators

• Jian Shen, MD,PhD · Second Affiliated Hospital, School of Medicine, Zhejiang University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

19 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-10

Primary Completion

2029-12-31

Completion

2033-05-31