Coronary Artery Disease
Conditions
Keywords
Percutaneous Coronary Intervention, De-Novo Coronary Lesion, Drug-Coated Balloon, High Bleeding Risk, Prognosis
Brief summary
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 in patients with high bleeding risk (HBR).
Detailed description
Second-generation 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 accompany 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 lead 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 metallic 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 RCT demonstrated efficacy and safety of DCB in de-novo coronary lesions in small vessels with reference vessel size\<3.0mm. However, studies exploring the feasibility of DCB in de-novo coronary artery stenosis beyond small vessels are limited. Furthermore, there is scarce data comparing DCB with DES in patients with de-novo coronary artery stenosis and high bleeding risk (HBR), a situation in which long-term maintenance of DAPT is a clinical dilemma. In previous BASKET-SMALL 2 trial, DCB showed noninferiority to DES in patients with de-novo coronary artery stenosis and small vessel disease. However, this trial was conducted in non-HBR patients, and the number of participated patients was insufficient. In another RCT, DEBUT trial exclusively enrolled patients with HBR and de-novo coronary artery stenosis. Although the DEBUT trial showed superiority of DCB angioplasty over implantation of BMS to treat de-novo coronary artery stenosis in patients with HBR, the results could not be applicable in contemporary practice because BMS has been no longer in clinical use. Recently, multiple RCTs have proved short-term DAPT (1-3 months) has comparable efficacy to longer term DAPT in HBR patients using latest second-generation DES. On this background, the current trial aims to compare clinical outcomes between DCB and DES to treat de-novo coronary artery stenosis in patients with HBR receiving guideline-directed short-term DAPT.
Interventions
PROCEDUREPercutaneous coronary intervention
1:1 randomization to DES (Ultimaster Tansei) or DCB (Agent \[Boston Scientific, USA\], Prevail \[Medtronic, USA\], or SeQuent Please, SeQuent Please NEO \[B-Braun, Germany\])
Sponsors
Samsung Medical Center
Seoul St. Mary's Hospital
Seoul National University Bundang Hospital
Korea University Ansan Hospital
Chonnam National University Hospital
Chung-Ang University Gwangmyeong Hospital
Gangneung Asan Hospital, University of Ulsan College of Medicine
Gyeongsang National University Hospital
Uijeongbu St. Mary Hospital
Keimyung University Dongsan Medical Center
Inha University Hospital
Chungbuk National University
Wonju Severance Christian Hospital
SMG-SNU Boramae Medical Center
Kangbuk Samsung Hospital, Sungkyunkwan University
Ewha Womans University
Korea University Guro Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Clinical outcome assessment will be performed under blinded assessment about the allocated treatment group.
Intervention model description
Prospective, multi-center, open-label, randomized controlled, noninferiority trial
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must be at least 19 years of age 2. Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily. 3. 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 4. 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 bleeding (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
1. Patients unable to provide consent 2. Patients with known intolerance to aspirin, P2Y12 inhibitors, or components of drug-eluting stents 3. 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 4. Patients who have non-cardiac co-morbid conditions with life expectancy \<2 year 5. Patients who may result in protocol non-compliance (site investigator's medical judgment) 6. Patients with cardiogenic shock or cardiac arrest 7. Patients with severe left ventricular systolic dysfunction (ejection fraction \<30%) 8. Patients with severe valvular heart disease requiring open heart surgery 9. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Target vessel failure (TVF) | 2 years from last patient enrollment | a composite of cardiovascular death, target-vessel myocardial infarction (MI), and clinically indicated target-vessel revascularization (TVR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target-vessel MI at Extended Follow-up | 4 years from last patient enrollment | Target-vessel MI at Extended Follow-up |
| Non-target vessel related MI at Extended Follow-up | 4 years from last patient enrollment | Non-target vessel related MI at Extended Follow-up |
| Non-fatal MI at Extended Follow-up | 4 years from last patient enrollment | Non-fatal MI at Extended Follow-up |
| Cardiovascular death, target-vessel MI, or vessel or stent thrombosis | 2 years from last patient enrollment | Cardiovascular death, target-vessel MI, or vessel or stent thrombosis |
| All-cause death, non-fatal MI, or any revascularization | 2 years from last patient enrollment | All-cause death, non-fatal MI, or any revascularization |
| Bleeding according to BARC definition | 2 years from last patient enrollment | Bleeding according to BARC definition |
| Bleeding according to TIMI definition | 2 years from last patient enrollment | Bleeding according to TIMI definition |
| Cerebrovascular accident (CVA) | 2 years from last patient enrollment | Ischemic stroke, Hemorrhagic stroke, Transient ischemic attack (TIA) |
| Target vessel failure (TVF) at Extended Follow-up | 4 years from last patient enrollment | a composite of cardiovascular death, target-vessel myocardial infarction (MI), and clinically indicated target-vessel revascularization (TVR) at Extended Follow-up |
| BARC type 2, 3 or 5 bleeding (Major secondary endpoint) at Extended Follow-up | 4 years from last patient enrollment | BARC type 2, 3 or 5 bleeding at Extended Follow-up |
| BARC type 2, 3 or 5 bleeding (Major secondary endpoint) | 2 years from last patient enrollment | BARC type 2, 3 or 5 bleeding |
| Cardiovascular death | 2 years from last patient enrollment | Cardiovascular death |
| All-cause death | 2 years from last patient enrollment | All-cause death |
| Target-vessel MI | 2 years from last patient enrollment | Target-vessel MI |
| Non-target vessel related MI | 2 years from last patient enrollment | Non-target vessel related MI |
| Non-fatal MI | 2 years from last patient enrollment | Non-fatal MI |
| Clinically indicated target-lesion revascularization (TLR) | 2 years from last patient enrollment | Clinically indicated target-lesion revascularization (TLR) |
| Clinically indicated TVR | 2 years from last patient enrollment | Clinically indicated TVR |
| Non-target vessel revascularization | 2 years from last patient enrollment | Non-target vessel revascularization |
| Any revascularization | 2 years from last patient enrollment | Any revascularization |
| Vessel or stent thrombosis | 2 years from last patient enrollment | definite by Academic Research Consortium (ARC) definition |
| Cardiovascular death or target-vessel MI | 2 years from last patient enrollment | Cardiovascular death or target-vessel MI |
| Target vessel failure without procedure-related MI | 2 years from last patient enrollment | a composite of cardiovascular death, target-vessel myocardial infarction (MI) without procedure-related MI, and clinically indicated target-vessel revascularization (TVR) |
| Target lesion failure (TLF) | 2 years from last patient enrollment | a composite of cardiovascular death, target-vessel MI, and clinically indicated TLR |
| Cardiovascular death at Extended Follow-up | 4 years from last patient enrollment | Cardiovascular death at Extended Follow-up |
| Clinically indicated target-lesion revascularization (TLR) at Extended Follow-up | 4 years from last patient enrollment | Clinically indicated target-lesion revascularization (TLR) at Extended Follow-up |
| Clinically indicated TVR at Extended Follow-up | 4 years from last patient enrollment | Clinically indicated TVR at Extended Follow-up |
| Non-target vessel revascularization at Extended Follow-up | 4 years from last patient enrollment | Non-target vessel revascularization at Extended Follow-up |
| Any revascularization at Extended Follow-up | 4 years from last patient enrollment | Any revascularization at Extended Follow-up |
| Vessel or stent thrombosis at Extended Follow-up | 4 years from last patient enrollment | definite ㅍessel or stent thrombosis at Extended Follow-up by Academic Research Consortium (ARC) definition |
| Target vessel failure without procedure-related MI at Extended Follow-up | 4 years from last patient enrollment | a composite of cardiovascular death, target-vessel myocardial infarction (MI) without procedure-related MI, and clinically indicated target-vessel revascularization (TVR) |
| Cardiovascular death or target-vessel MI at Extended Follow-up | 4 years from last patient enrollment | Cardiovascular death or target-vessel MI at Extended Follow-up |
| Target lesion failure (TLF) at Extended Follow-up | 4 years from last patient enrollment | Target lesion failure (TLF) at Extended Follow-up |
| Cardiovascular death, target-vessel MI, or vessel or stent thrombosis at Extended Follow-up | 4 years from last patient enrollment | Cardiovascular death, target-vessel MI, or vessel or stent thrombosis at Extended Follow-up |
| All-cause death, non-fatal MI, or any revascularization at Extended Follow-up | 4 years from last patient enrollment | All-cause death, non-fatal MI, or any revascularization at Extended Follow-up |
| Bleeding according to BARC definition at Extended Follow-up | 4 years from last patient enrollment | Bleeding according to BARC definition at Extended Follow-up |
| Bleeding according to TIMI definition at Extended Follow-up | 4 years from last patient enrollment | Bleeding according to TIMI definition at Extended Follow-up |
| All-cause death at Extended Follow-up | 4 years from last patient enrollment | All-cause death at Extended Follow-up |
| Cerebrovascular accident (CVA) at Extended Follow-up | 4 years from last patient enrollment | Ischemic stroke, Hemorrhagic stroke, Transient ischemic attack (TIA) |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORJoo Myung Lee, MD, PhD
Samsung Medical Center
Outcome results
None listed