Drug-Coated Balloon in Patients With High Bleeding Risk

Study Overview
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Brief Summary
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DCB-HBR trial is prospective, multi-center, open-label, randomized controlled, noninferiority trial. The aim of the study is to compare clinical outcomes of drug-coated balloon (DCB) with drug-eluting stent (DES) for treatment of de-novo coronary lesion under intravascular imaging-guided optimization in patients with high bleeding risk (HBR).

Detailed Description
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Second-generation drug-eluting stent (DES) is the standard of care for patients with coronary artery disease who are deemed eligible for percutaneous coronary intervention (PCI). Despite many advantages, DES inevitably accompanies disadvantages such as the occurrence of late stent thrombosis and the need for maintaining dual antiplatelet (DAPT) for certain period due to permanent vascular implant, which leads to both increased ischemic and bleeding events. As an alternative to DES, drug-coated balloon (DCB), a novel treatment strategy, which has benefit of having shorter DAPT maintenance duration due to the absence of scaffolds and polymers, has been introduced. Based on meta-analysis based on many randomized clinical trials (RCT), its use has been established in in-stent restenosis of bare-metal stents (BMS) and DES. Furthermore, recently published RCTs demonstrated efficacy and safety of DCB in de-novo coronary lesions in small vessels. However, studies exploring the feasibility of DCB in de-novo coronary lesions are limited. In particular, there are scarce data comparing DCB with DES in patients with high bleeding risk (HBR), a situation in which long-term maintenance of DAPT is a clinical dilemma. In the previous two RCTs, DCB showed noninferiority to DES in lesions in large vessels. Nevertheless, these studies were conducted in non-HBR patients and the number of participated patients was insufficient. In another RCT, only patients with HBR were included, but the efficacy of DCB was compared with BMS not DES. Recently, studies have proved short term (1-3 months) DAPT has comparable efficacy to longer DAPT in HBR patients using latest second-generation DES. On this background, this trial aims to compare clinical outcomes between DCB and DES in de-novo coronary lesions in large vessels in patients with HBR receiving short term DAPT.

Official Title
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Drug-Coated Balloon Versus Drug-Eluting Stent for Treatment of De-Novo Coronary Lesions in Patients With High Bleeding Risk

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: Percutaneous coronary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 19 years of age Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily. Patients with at least one lesion with greater than 50% diameter stenosis or fractional flow reserve ≤0.80 requiring revascularization in de-novo coronary artery of reference vessel size ≥2.25 mm Patients with high bleeding risk: one or more of the criteria listed (1) Adjunctive oral anticoagulation treatment planned to continue after PCI (2) Age ≥ 75 years old (3) Baseline Hemoglobin <11 g/dl (or anemia requiring transfusion during the 4 weeks prior to randomization) (4) Any prior intra-cerebral bleed (5) Stroke at any time or transient ischemic attack in the previous 6 months. (6) Hospital admission for bleeding during the prior 12 months (7) Non skin cancer diagnosed or treated < 3 years (8) Planned daily NSAID (other than aspirin) or steroids for >30 days after PCI (9) Planned surgery that would require interruption of DAPT (within next 12 months) (10) Renal failure defined as calculated creatinine clearance <40 ml/min or on dialysis (11) Hematological disorders (platelet count <100,000/mm3 or any coagulation disorder) (12) Severe chronic liver disease defined as patients who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy or jaundice (13) Expected non-compliance to prolonged DAPT for other medical reasons Exclusion Criteria: Patients unable to provide consent Patients with known intolerance to aspirin, P2Y12 inhibitors, or components of drug-eluting stents Patients with angiographic findings of (1) Left main coronary artery disease (2) In-stent restenosis is the cause of target lesion (3) Target lesion in bypass graft (4) True bifurcation lesion that requires upfront 2-stenting Patients who have non-cardiac co-morbid conditions with life expectancy <2 year Patients who may result in protocol non-compliance (site investigator's medical judgment) Patients with cardiogenic shock or cardiac arrest Patients with severe left ventricular systolic dysfunction (ejection fraction <30%) Patients with severe valvular heart disease requiring open heart surgery Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: Prospective, multi-center, open-label, randomized controlled, noninferiority trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DES group<br>Patients will be randomized to either the DCB group or the DES group with 1:1 ratio during the index procedure after diagnostic angiography. In DES group, latest second-generation DES will be used (Ultimaster Tansei) during the index procedure | Procedure: Percutaneous coronary intervention<br>* 1:1 randomization to DES (Ultimaster Tansei) or DCB (Agent [Boston Scientific, USA], Prevail [Medtronic, USA], or SeQuent Please, SeQuent Please NEO [B-Braun, Germany])<br>|
| Experimental: DCB group<br>Patients will be randomized to either the DCB group or the DES group with 1:1 ratio during the index procedure after diagnostic angiography. In DCB group, Agent (Boston Scientific, USA), Prevail (Medtronic, USA), or SeQuent Please, SeQuent Please NEO (B-Braun, Germany) will be used during the index procedure. | Procedure: Percutaneous coronary intervention<br>* 1:1 randomization to DES (Ultimaster Tansei) or DCB (Agent [Boston Scientific, USA], Prevail [Medtronic, USA], or SeQuent Please, SeQuent Please NEO [B-Braun, Germany])<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target vessel failure (TVF) | a composite of cardiovascular death, target-vessel myocardial infarction (MI), and clinically indicated target-vessel revascularization (TVR) | 2 years from last patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death | Cardiovascular death | 2 years from last patient enrollment | 
| All-cause death | All-cause death | 2 years from last patient enrollment | 
| Target-vessel MI | Target-vessel MI | 2 years from last patient enrollment | 
| Non-fatal MI | Non-fatal MI | 2 years from last patient enrollment | 
| Clinically indicated target-lesion revascularization (TLR) | Clinically indicated target-lesion revascularization (TLR) | 2 years from last patient enrollment | 
| Clinically indicated TVR | Clinically indicated TVR | 2 years from last patient enrollment | 
| Any revascularization | Any revascularization | 2 years from last patient enrollment | 
| Vessel or stent thrombosis | definite or probable by Academic Research Consortium (ARC) definition | 2 years from last patient enrollment | 
| Cardiovascular death or target-vessel MI | Cardiovascular death or target-vessel MI | 2 years from last patient enrollment | 
| All-cause death or non-fatal MI | All-cause death or non-fatal MI | 2 years from last patient enrollment | 
| Target lesion failure (TLF) | a composite of cardiovascular death, target-vessel MI, and clinically indicated TLR | 2 years from last patient enrollment | 
| Cardiovascular death, target-vessel MI, or vessel or stent thrombosis | Cardiovascular death, target-vessel MI, or vessel or stent thrombosis | 2 years from last patient enrollment | 
| All-cause death, non-fatal MI, or TVR | All-cause death, non-fatal MI, or TVR | 2 years from last patient enrollment | 
| Major bleeding (Major secondary endpoint) | BARC type 2, 3 or 5 bleeding | 2 years from last patient enrollment | 
| Major bleeding | The Thrombolysis in Myocardial Infarction (TIMI) major bleeding | 2 years from last patient enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous Coronary Intervention, De-Novo Coronary Lesion, Drug-Coated Balloon, High Bleeding Risk, Prognosis