Drug-Coated Balloon vs. Drug-Eluting Stent for Clinical Outcomes in Patients With Large Coronary Artery Disease

Study Overview
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Brief Summary
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Prospective, randomised, open-label, international multicenter trial to evaluate the safety and efficacy of drug-coated balloon (DCB) treatment compared to drug-eluting stenting (DES) in patients with large coronary artery disease.

Detailed Description
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Although several reports suggested that DCB application was safe for larger coronary artery lesions and showed good long-term outcomes, there is limited randomised controlled trial (RCT) data on the safety and efficacy of DCB in large coronary artery disease. Therefore, the study aims to demonstrate the non-inferiority of the drug-coated balloon (DCB) treatment against current-generation drug-eluting stenting (DES) in patients with de novo lesions in large coronary artery disease (reference vessel diameter ≥3.0 mm by visual estimation). The hypothesis of the study is the clinical outcomes of patients treated with DCB are non-inferior to those treated with current-generation DES.

Official Title
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Randomised Trial of Drug-Coated Balloon Versus Drug-Eluting Stent for Clinical Outcomes in Patients With Large Coronary Artery Disease

Conditions
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Coronary Artery Disease, Myocardial Ischemia, Acute Coronary Syndrome, Coronary Stenosis, De Novo Stenosis

Intervention / Treatment
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* Device: SeQuent® Please NEO drug-coated balloon catheter
* Device: Current-generation drug-eluting stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient-related: Patient must be ≥ 18 years of age Patient is able to verbally confirm understanding of the study aim, risks, benefits, and treatment alternatives of receiving DCB or DES and he/she or his/her legally authorized representative provides written informed consent prior to any study-related procedure (i) Clinical evidence of angina, and/or (ii) an abnormal functional study demonstrating myocardial ischemia due to the target lesion(s), or (iii) acute coronary syndrome [unstable angina or non-ST-elevation myocardial infarction (NSTEMI) or uneventful STEMI (≥ 48 hours after primary PCI and no sign of thrombus in lesion(s) to treat)] Patient with lesions suitable for PCI with a DCB (and/or DES) according to the Instructions for Use Patient is able to comply with the study protocol and agrees to undergo the clinical follow-up of 30 days, 6 months, 12 months, 24 months, and 36 months Lesion-related: Presence of significant de novo large vessel coronary artery disease (reference vessel diameter ≥3.0 mm by visual estimation) with either ≥ 70% diameter stenosis or intermediate ≥ 50% to <70% diameter stenosis with abnormal functional test or symptom of ischemia Successful lesion preparation. For randomisation, the lesion must satisfy the following criteria after optimal balloon angioplasty: no flow-limiting dissection (TIMI=3), and residual stenosis is ≤ 30% Multivessel disease with two or more vessels showing diameter stenosis of 50% or more is not an exclusion as long as it fulfills all study's eligibility criteria. In diffuse lesion, inclusion is possible if the proximal reference vessel diameter is 3.0 mm or more. Exclusion Criteria: Patient-related: Intolerance or allergy to Paclitaxel and/or the delivery matrix (main ingredient: Iopromide) Severe allergy to contrast media Recent STEMI (ongoing or < 48 hours after primary PCI and/or has sign of thrombus in lesion(s) to treat) NSTEMI hemodynamically unstable Known left ventricular ejection fraction of <30% Inability to take dual antiplatelet therapy or anticoagulation, or single antiplatelet therapy for at least six months Non-cardiac co-morbid conditions that may result in protocol non-compliance and inability of patient to complete the study (per the site investigator's medical judgment) Patient with concomitant medical illnesses that require cytostatic, radiation therapy or renal replacement therapy Patient who is currently/ planning to participate in another clinical trial when such participation could confound the treatment or outcomes of this study, except for observational registry Pregnancy or lactation Patient under administrative or judicial custody Lesion-related: Small vessel disease, defined as <3.0 mm of reference vessel diameter by visual estimation In-stent restenosis lesions for study lesions Patient will be excluded if meet any of the following angiographic exclusion criteria after lesion preparation: (i) Flow limiting dissection with TIMI flow < III (ii) Residual diameter stenosis >30% * The case of persistent ischemic symptoms/signs is up to the operator's decision Lesions which are untreatable with PCI or other interventional techniques and coronary artery spasm in the absence of a significant stenosis Left main disease or aorta-ostial lesion requiring revascularization Severely calcified or tortuous vessels precluding DCB or DES application Prior Coronary Artery Bypass Graft (CABG)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SeQuent® Please NEO drug-coated balloon catheter<br> | Device: SeQuent® Please NEO drug-coated balloon catheter<br>* Treatment of coronary artery disease with SeQuent® Please NEO for de novo lesions in native large coronary arteries<br>|
| Experimental: Current-generation drug-eluting stent<br> | Device: Current-generation drug-eluting stent<br>* Treatment of coronary artery disease with current-generation drug-eluting stent for de novo lesions in native large coronary arteries<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net Adverse Clinical Event (NACE) | Net adverse clinical event (NACE): a composite of all-cause death, non-fatal myocardial infarction, clinically driven target vessel revascularization, or major bleeding (BARC type 3 to 5) | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death |  | At 12, 24, and 36 months | 
| Non-fatal myocardial infarction |  | At 12, 24, and 36 months | 
| Clinically driven target vessel revascularization |  | At 12, 24, and 36 months | 
| Major bleeding (BARC type 3 to 5) |  | At 12, 24, and 36 months | 
| Cardiac death |  | At 12, 24, and 36 months | 
| Target vessel myocardial infarction |  | At 12, 24, and 36 months | 
| Periprocedural myocardial infarction |  | At 12, 24, and 36 months | 
| Target lesion revascularization |  | At 12, 24, and 36 months | 
| Stent/lesion thrombosis in treated lesion defined according to the Academic Research Consortium-2 (ARC-2) criteria |  | At 12, 24, and 36 months | 
| Rehospitalization related to study endpoints | Rate of hospitalization related to study endpoints | At 30 days, 12 months, 24 months, and 36 months | 
| Stroke (ischemic and hemorrhagic) | Number of participants with stroke (ischemic and hemorrhagic) | At 12, 24, and 36 months | 
| Total angioplasty procedure time |  | During the index procedure | 
| Fluoroscopy time of the angioplasty procedure |  | During the index procedure | 
| Contrast volume of the angioplasty procedure |  | During the index procedure | 
| Number of devices (DCB/ DES) used for PCI treatment |  | During the index procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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de novo, large vessel, coronary artery disease, cardiovascular disease, coronary occlusion, heart disease, acute coronary syndrome, angina, ischemia, stenosis, percutaneous coronary intervention, angioplasty, drug-coated balloon, drug-eluting stent, SeQuent Please, randomised trial