Coronary Artery DiseaseLARGENCT07548281
Intravascular Ultrasound- and Angiography-Derived Fractional Flow Reserve-Guided Drug-Coated Balloon for Large Coronary Artery De Novo Lesions
A study testing DCB in large de novo coronary lesions guided by IVUS and AngioFFR and DES in large de novo coronary lesions guided by IVUS and AngioFFR in people with Coronary Artery Disease, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- DCB in large de novo coronary lesions guided by IVUS and AngioFFR and DES in large de novo coronary lesions guided by IVUS and AngioFFR
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,492 participants
- Where
- No sites listed yet
- Study dates
- 10 Apr 2026to 31 May 2033
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- Following adequate intraoperative lesion preparation, the following must be met: IVUS shows MLA≥ 4.0mm² and/or AnioFFR > 0.80.
- Absence of flow-limiting dissection or hematoma (angiographic Type A or B dissection; IVUS dissection not involving the media) and TIMI flow grade 3
- Patients must be able to be followed up for more than 1 year and be willing to cooperate with the trial follow-up requirements.
Who cannot join
- Patients younger than 19 or older than 80 years of age.
- 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.
- Recent major surgery (within 1 month pre-procedure) or clear gastrointestinal bleeding events.
- 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).
- Women who are currently pregnant or breastfeeding.
- Non-cardiac comorbidities indicating an expected life expectancy of less than 1 year.
- Any other factors that may affect follow-up or participation in other clinical studies.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read more
Inclusion Criteria
- 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.
- 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.
- Following adequate intraoperative lesion preparation, the following must be met: IVUS shows MLA≥ 4.0mm² and/or AnioFFR > 0.80.
- Absence of flow-limiting dissection or hematoma (angiographic Type A or B dissection; IVUS dissection not involving the media) and TIMI flow grade 3
- 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
- Patients are younger than 19 or older than 80 years of age.
- 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.
- Recent major surgery (within 1 month pre-procedure) or clear gastrointestinal bleeding events.
- 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).
- Women who are currently pregnant or breastfeeding.
- Non-cardiac comorbidities indicating an expected life expectancy of less than 1 year.
- 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
- Target Vessel Failure (TVF): A composite of cardiac death, target vessel MI, or target vessel revascularization.
- NACE, major bleeding or clinically relevant non-major bleeding, and MACCE at 36 and 60 months.
- All-cause death and cardiac death.
- MI, spontaneous MI, peri-procedural MI, and target vessel MI.
- Any revascularization of the target vessel/target lesion.
- Any revascularization of a non-target vessel/ non-target lesion.
- Any revascularization (ischemia-driven or all-cause).
- Stent Thrombosis: Classified as definite, probable, or possible.
- Stroke: Including both ischemic and hemorrhagic stroke.
- Bleeding Events: BARC 3 or 5 bleeding, and BARC 2 bleeding.
- Evaluation of cost-effectiveness.
Read the detailed description
Background Coronary artery disease (CAD) remains a leading cause of death and disability worldwide. While the widespread use of percutaneous coronary intervention (PCI) and drug-eluting stents (DES) has significantly improved patient outcomes, long-term follow-up studies indicate that stent-related complications, such as late restenosis, very late thrombosis, decreased vascular compliance due to metal residue, and high bleeding risks associated with long-term dual antiplatelet therapy (DAPT), remain significant concerns.
In this context, the drug-coated balloon (DCB) has emerged as a "metal-free" alternative strategy. By expanding the balloon to release anti-proliferative drugs directly into the vessel wall, DCBs aim to reduce metal residue, improve vascular healing, and lower the incidence of long-term events. "Intervention without implantation" represents the future direction of coronary intervention.
Internationally, multiple high-quality studies have validated the safety and efficacy of DCB in treating in-stent restenosis (ISR) and small vessel de novo lesions. For instance, international DCB consensus clearly includes ISR and small vessel disease within mature indications. Recent research has shown that in small vessel disease, DCB is comparable to second-generation DES in terms of target lesion revascularization (TLR) and major adverse cardiovascular events (MACE), while offering lower long-term stent-related risks.
Current DCB research is gradually expanding toward "large coronary artery de novo lesions". These lesions typically involve a reference vessel diameter ≥2.75-3.0 mm, high plaque burden, and poor vascular compliance. Some international studies have found that under conditions of adequate lesion preparation (residual stenosis < 30%, absence of severe dissection, and sufficient expansion), DCB treatment for large vessel de novo lesions can achieve satisfactory results. However, a multicenter randomized controlled trial of 2,272 patients showed a 3-year composite endpoint of 8.2% for DCB (plus rescue stenting) versus 5.0% for DES, suggesting that in unselected patient populations, DCB did not meet non-inferiority standards compared to DES. Currently, there is a lack of large-scale randomized controlled trials specifically investigating DCB intervention for large de novo lesions.
Previous studies have demonstrated that Intravascular Ultrasound (IVUS) and Angiography-Derived Fractional Flow Reserve (AngioFFR) effectively improve patient outcomes, with both technologies receiving Class I recommendations in multiple international guidelines. Our research team previously analyzed 610 cases of DCB treatment guided by IVUS combined AngioFFR. For coronary arteries with a diameter ≥2.75 mm, patients who achieved a post-preprocessing minimal lumen area (MLA) ≥ 4.0 mm2 and AngioFFR > 0.80, without flow-limiting dissection, showed favorable outcomes with a 1-year follow-up event rate of less than 10%. Therefore, exploring the efficacy of DCB in large coronary artery de novo lesions guided by coronary imaging and functional physiology is of great significance.
Currently, for DCB treatment of small vessels and ISR, DAPT is typically maintained for only 1-3 months. However, there is no clear guideline-recommended antiplatelet strategy for large de novo lesions. Based on the regenerative and repair functions of the vascular endothelium, endothelialization of the treated lesion can be completed within 1 month post-procedure, supporting a de-escalation antiplatelet strategy. Consequently, further exploration of antiplatelet strategies for large de novo lesion patients treated with DCB is highly important.
Hypothesis
This study employs a hierarchical testing (sequential testing) approach. The hypotheses will be tested in the following order:
In patients with large coronary artery de novo lesions, under the guidance of IVUS and AngioFFR:
H1: The DCB treatment group is non-inferior to the DES treatment group regarding Net Adverse Clinical Events (NACE) at 12 months.
H2: The DCB group is non-inferior to the DES group regarding Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 12 months.
H3: The DCB group is superior to the DES group regarding major bleeding or clinically relevant non-major bleeding (BARC 2, 3, or 5) at 12 months.
- DCB Treatment Group Patients receive Dual Antiplatelet Therapy (DAPT) for 1 month. After 1 month, therapy is switched to Single Antiplatelet Therapy (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.
- DES Treatment Group 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 Device Selection: The specific type of DCB or DES used is at the operator's discretion.
Medication Selection: The specific types of drugs used for DAPT or SAPT are determined by the operator.
Study Period Seven years after IRB approval
- Conditions
- Coronary Artery Disease
- Being tested
- DCB in large de novo coronary lesions guided by IVUS and AngioFFR, DES in large de novo coronary lesions guided by IVUS and AngioFFR
- Keywords
- Drug-coated balloon, De novo large vessel lesion, Intravascular ultrasound, Angiography-derived fractional flow reserve, Percutaneous coronary intervention, coronary artery disease
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DCB in large de novo coronary lesions guided by IVUS and AngioFFRDevice
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.
DES in large de novo coronary lesions guided by IVUS and AngioFFRDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| DCB Treatment Group | Experimental | Drug-Coated Balloons (DCB) in large de novo coronary lesions Receives: Device: DCB in large de novo coronary lesions guided by IVUS and AngioFFR |
| DES Treatment Group | Active comparator | Drug-Eluting Stents (DES) in large de novo coronary lesions Receives: Device: DES in large de novo coronary lesions guided by IVUS and AngioFFR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net Adverse Clinical Events (NACE)
Cumulative incidence of death, stroke, myocardial infarction (MI), ischemia-driven revascularization, or bleeding (BARC 3 or 5). Scale: %
Measured: 12 months after the procedure
Ischemic Endpoint - Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Cumulative incidence of death, MI, ischemia-driven revascularization, or ischemic stroke. Scale: %
Measured: 12 months after the procedure
Bleeding Endpoint
Cumulative incidence of major bleeding or clinically relevant non-major bleeding, categorized as BARC 2, 3, or 5. Scale: %
Measured: 12 months after the procedure
Secondary outcomes (10)
Net Adverse Clinical Events (NACE)
Cumulative incidence of all-cause death, stroke, myocardial infarction (MI), ischemia-driven revascularization, or bleeding (BARC 3 or 5). Scale: %
Measured: 36 and 60 months after the procedure
2. Ischemic Endpoint - Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Cumulative incidence of death, MI, ischemia-driven revascularization, or ischemic stroke. Scale: %
Measured: 36, 60 months after the procedure
Bleeding Events
Cumulative incidence of major bleeding or clinically relevant non-major bleeding, categorized as BARC 2, 3, or 5. Scale: %
Measured: 36, 60 months after the procedure
Target Vessel Failure (TVF)
Cumulative incidence of cardiac death, target vessel MI, or target vessel revascularization. Scale: %
Measured: 12, 36, 60 months after the procedure
All-cause death and cardiac death
Cumulative incidence of all-cause death and cardiac death. Scale: %
Measured: 12, 36, 60 months after the procedure
MI, spontaneous MI, peri-procedural MI, and target vessel MI
Cumulative incidence of MI, spontaneous MI, peri-procedural MI, and target vessel MI. Scale: %
Measured: 12, 36, 60 months after the procedure
Any revascularization of the target vessel/target lesion.
Cumulative incidence of target vessel/target lesion revascularization. Scale: %
Measured: 12, 36, 60 months after the procedure
Any revascularization (ischemia-driven or all-cause)
Cumulative incidence of ischemia-driven or all-cause revascularization. Scale: %.
Measured: 12, 36, 60 months after the procedure
Stent Thrombosis
Cumulative incidence of stent thrombosis (definite, probable, or possible). Scale: %.
Measured: 12, 36, 60 months after the procedure
Stroke
Cumulative incidence of stroke (ischemic and hemorrhagic). Scale: %
Measured: 12, 36, 60 months after the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2026
- Study start10 Apr 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 May 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 2,492 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Ulsan University Hospital, Shanghai Zhongshan Hospital, First Affiliated Hospital of Wenzhou Medical University, The First People's Hospital of Huzhou, Huzhou Central Hospital, First Affiliated Hospital of Ningbo University, Ningbo Medical Center Lihuili Hospital, Yiwu Central Hospital, People's Hospital of Quzhou, Lishui Country People's Hospital, First Affiliated Hospital of Guangxi Medical University, First People's Hospital of Yulin, Longyan City First Hospital, Fourth Affiliated Hospital of Xinjiang Medical University, Shangrao People's Hospital, Fuyang people's hospital, First People's Hospital of Xianyang, The First People's Hospital of Yunnan
- Responsible party
- Sponsor
- Investigators
- Jian Shen, MD,PhD, Principal investigator, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07548281
- Sponsor's protocol ID
- 2026-0258
- Acronym
- LARGE
- Status last verified
- Mar 2026
- First submitted
- 9 Apr 2026
- Last updated
- 23 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices), will be shared. The data will be available following primary article publication. Data will be shared with researchers who provide a methodologically sound proposal to PIs.
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravascular Ultrasound- and Angiography-Derived Fractional Flow Reserve-Guided Drug-Coated Balloon for Large Coronary Artery De Novo Lesions
- ClinicalTrials.gov ID
- NCT07548281
- Acronym / sponsor ID
- LARGE / 2026-0258
- Conditions
- Coronary Artery Disease
- Keywords
- Drug-coated balloon, De novo large vessel lesion, Intravascular ultrasound, Angiography-derived fractional flow reserve, Percutaneous coronary intervention, coronary artery disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 2,492 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Ulsan University Hospital, Shanghai Zhongshan Hospital, First Affiliated Hospital of Wenzhou Medical University, The First People's Hospital of Huzhou, Huzhou Central Hospital, First Affiliated Hospital of Ningbo University, Ningbo Medical Center Lihuili Hospital, Yiwu Central Hospital, People's Hospital of Quzhou, Lishui Country People's Hospital, First Affiliated Hospital of Guangxi Medical University, First People's Hospital of Yulin, Longyan City First Hospital, Fourth Affiliated Hospital of Xinjiang Medical University, Shangrao People's Hospital, Fuyang people's hospital, First People's Hospital of Xianyang, The First People's Hospital of Yunnan
- Study start
- 10 Apr 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 May 2033 (estimated)
- First posted
- 23 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
- 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.
- Following adequate intraoperative lesion preparation, the following must be met: IVUS shows MLA≥ 4.0mm² and/or AnioFFR > 0.80.
- Absence of flow-limiting dissection or hematoma (angiographic Type A or B dissection; IVUS dissection not involving the media) and TIMI flow grade 3
- 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
- Patients are younger than 19 or older than 80 years of age.
- 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.
- Recent major surgery (within 1 month pre-procedure) or clear gastrointestinal bleeding events.
- 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).
- Women who are currently pregnant or breastfeeding.
- Non-cardiac comorbidities indicating an expected life expectancy of less than 1 year.
- 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
- Target Vessel Failure (TVF): A composite of cardiac death, target vessel MI, or target vessel revascularization.
- NACE, major bleeding or clinically relevant non-major bleeding, and MACCE at 36 and 60 months.
- All-cause death and cardiac death.
- MI, spontaneous MI, peri-procedural MI, and target vessel MI.
- Any revascularization of the target vessel/target lesion.
- Any revascularization of a non-target vessel/ non-target lesion.
- Any revascularization (ischemia-driven or all-cause).
- Stent Thrombosis: Classified as definite, probable, or possible.
- Stroke: Including both ischemic and hemorrhagic stroke.
- Bleeding Events: BARC 3 or 5 bleeding, and BARC 2 bleeding.
- Evaluation of cost-effectiveness.
Detailed description
Background Coronary artery disease (CAD) remains a leading cause of death and disability worldwide. While the widespread use of percutaneous coronary intervention (PCI) and drug-eluting stents (DES) has significantly improved patient outcomes, long-term follow-up studies indicate that stent-related complications, such as late restenosis, very late thrombosis, decreased vascular compliance due to metal residue, and high bleeding risks associated with long-term dual antiplatelet therapy (DAPT), remain significant concerns.
In this context, the drug-coated balloon (DCB) has emerged as a "metal-free" alternative strategy. By expanding the balloon to release anti-proliferative drugs directly into the vessel wall, DCBs aim to reduce metal residue, improve vascular healing, and lower the incidence of long-term events. "Intervention without implantation" represents the future direction of coronary intervention.
Internationally, multiple high-quality studies have validated the safety and efficacy of DCB in treating in-stent restenosis (ISR) and small vessel de novo lesions. For instance, international DCB consensus clearly includes ISR and small vessel disease within mature indications. Recent research has shown that in small vessel disease, DCB is comparable to second-generation DES in terms of target lesion revascularization (TLR) and major adverse cardiovascular events (MACE), while offering lower long-term stent-related risks.
Current DCB research is gradually expanding toward "large coronary artery de novo lesions". These lesions typically involve a reference vessel diameter ≥2.75-3.0 mm, high plaque burden, and poor vascular compliance. Some international studies have found that under conditions of adequate lesion preparation (residual stenosis < 30%, absence of severe dissection, and sufficient expansion), DCB treatment for large vessel de novo lesions can achieve satisfactory results. However, a multicenter randomized controlled trial of 2,272 patients showed a 3-year composite endpoint of 8.2% for DCB (plus rescue stenting) versus 5.0% for DES, suggesting that in unselected patient populations, DCB did not meet non-inferiority standards compared to DES. Currently, there is a lack of large-scale randomized controlled trials specifically investigating DCB intervention for large de novo lesions.
Previous studies have demonstrated that Intravascular Ultrasound (IVUS) and Angiography-Derived Fractional Flow Reserve (AngioFFR) effectively improve patient outcomes, with both technologies receiving Class I recommendations in multiple international guidelines. Our research team previously analyzed 610 cases of DCB treatment guided by IVUS combined AngioFFR. For coronary arteries with a diameter ≥2.75 mm, patients who achieved a post-preprocessing minimal lumen area (MLA) ≥ 4.0 mm2 and AngioFFR > 0.80, without flow-limiting dissection, showed favorable outcomes with a 1-year follow-up event rate of less than 10%. Therefore, exploring the efficacy of DCB in large coronary artery de novo lesions guided by coronary imaging and functional physiology is of great significance.
Currently, for DCB treatment of small vessels and ISR, DAPT is typically maintained for only 1-3 months. However, there is no clear guideline-recommended antiplatelet strategy for large de novo lesions. Based on the regenerative and repair functions of the vascular endothelium, endothelialization of the treated lesion can be completed within 1 month post-procedure, supporting a de-escalation antiplatelet strategy. Consequently, further exploration of antiplatelet strategies for large de novo lesion patients treated with DCB is highly important.
Hypothesis
This study employs a hierarchical testing (sequential testing) approach. The hypotheses will be tested in the following order:
In patients with large coronary artery de novo lesions, under the guidance of IVUS and AngioFFR:
H1: The DCB treatment group is non-inferior to the DES treatment group regarding Net Adverse Clinical Events (NACE) at 12 months.
H2: The DCB group is non-inferior to the DES group regarding Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 12 months.
H3: The DCB group is superior to the DES group regarding major bleeding or clinically relevant non-major bleeding (BARC 2, 3, or 5) at 12 months.
- DCB Treatment Group Patients receive Dual Antiplatelet Therapy (DAPT) for 1 month. After 1 month, therapy is switched to Single Antiplatelet Therapy (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.
- DES Treatment Group 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 Device Selection: The specific type of DCB or DES used is at the operator's discretion.
Medication Selection: The specific types of drugs used for DAPT or SAPT are determined by the operator.
Study Period Seven years after IRB approval
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DCB Treatment Group | Experimental | Device: DCB in large de novo coronary lesions guided by IVUS and AngioFFRDrug-Coated Balloons (DCB) in large de novo coronary lesions |
| DES Treatment Group | Active comparator | Device: DES in large de novo coronary lesions guided by IVUS and AngioFFRDrug-Eluting Stents (DES) in large de novo coronary lesions |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
- 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.
- Following adequate intraoperative lesion preparation, the following must be met: IVUS shows MLA≥ 4.0mm² and/or AnioFFR > 0.80.
- Absence of flow-limiting dissection or hematoma (angiographic Type A or B dissection; IVUS dissection not involving the media) and TIMI flow grade 3
- Patients must be able to be followed up for more than 1 year and be willing to cooperate with the trial follow-up requirements.
Key exclusion criteria (7 listed)
- Patients younger than 19 or older than 80 years of age.
- 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.
- Recent major surgery (within 1 month pre-procedure) or clear gastrointestinal bleeding events.
- 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).
- Women who are currently pregnant or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DCB in large de novo coronary lesions guided by IVUS and AngioFFRVisual 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 | DCB Treatment Group |
| DES in large de novo coronary lesions guided by IVUS and AngioFFRVisual 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. | Device | DES Treatment Group |
Primary outcome
Net Adverse Clinical Events (NACE)
Time frame: 12 months after the procedure
Cumulative incidence of death, stroke, myocardial infarction (MI), ischemia-driven revascularization, or bleeding (BARC 3 or 5). Scale: %
Ischemic Endpoint - Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Time frame: 12 months after the procedure
Cumulative incidence of death, MI, ischemia-driven revascularization, or ischemic stroke. Scale: %
Bleeding Endpoint
Time frame: 12 months after the procedure
Cumulative incidence of major bleeding or clinically relevant non-major bleeding, categorized as BARC 2, 3, or 5. Scale: %
10 secondary outcomes
Net Adverse Clinical Events (NACE)
Time frame: 36 and 60 months after the procedure
2. Ischemic Endpoint - Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Time frame: 36, 60 months after the procedure
Bleeding Events
Time frame: 36, 60 months after the procedure
Target Vessel Failure (TVF)
Time frame: 12, 36, 60 months after the procedure
All-cause death and cardiac death
Time frame: 12, 36, 60 months after the procedure
MI, spontaneous MI, peri-procedural MI, and target vessel MI
Time frame: 12, 36, 60 months after the procedure
Any revascularization of the target vessel/target lesion.
Time frame: 12, 36, 60 months after the procedure
Any revascularization (ischemia-driven or all-cause)
Time frame: 12, 36, 60 months after the procedure
Stent Thrombosis
Time frame: 12, 36, 60 months after the procedure
Stroke
Time frame: 12, 36, 60 months after the procedure
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices), will be shared. The data will be available following primary article publication. Data will be shared with researchers who provide a methodologically sound proposal to PIs.
Related trials for Coronary Artery Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jian Shen, MD,PhD principal investigator
Second Affiliated Hospital, Zhejiang University, School of Medicine
Questions about this trial
What is this clinical trial studying?
A study testing DCB in large de novo coronary lesions guided by IVUS and AngioFFR and DES in large de novo coronary lesions guided by IVUS and AngioFFR in people with Coronary Artery Disease, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
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 5 inclusion and 7 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: opening soon, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
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 Jian'an Wang, MD,PhD (+86 0571-87783759, wangjianan111@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Net Adverse Clinical Events (NACE) (time frame: 12 months after the procedure). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2026.