Drug-Coated Balloon in Anticoagulated and Bleeding Risk Patients Undergoing PCI
- Conditions
- Coronary Artery Disease
- Interventions
- Device: Percutaneous coronary intervention using drug-coated balloonDevice: Percutaneous coronary intervention using drug-eluting stent
- Registration Number
- NCT04814212
- Lead Sponsor
- North Karelia Central Hospital
- Brief Summary
The purpose of this study is to compare DCB with DES in stable CAD or ACS patients who are at high risk of bleeding. The hypothesis of the DEBATE trial is that the strategy using DCB and a shorter DAPT regimen is non-inferior to the treatment using DES and longer DAPT duration on patients with high bleeding risk. If non-inferiority is shown, the superiority of the DCB strategy over DES strategy will be tested.
- Detailed Description
Implantation of a drug-eluting stent (DES) has become a standard of percutaneous coronary intervention (PCI) during the last two decades. However there are still significant drawbacks in using DES as a permanent coronary implant. Most importantly, bleeding remains a significant complication of PCI, especially in elderly patients. The number of PCI patients having OAC:s is already significant, and will grow in the future, as the volume of PCIs in octogenarians increases, and so does the incidence of atrial fibrillation by age. After stenting at least one month lasting dual antiplatlet treatment (DAPT) is mandatory, and it cannot be safely terminated in case of a bleed. The optimal duration of DAPT on patients at bleeding risk is not known.
Balloon coated with paclitaxel and iopromide (drug-coated balloon, DCB) was originally developed for the treatment of in-stent restenosis, but later its potential for the treatment of de-novo coronary artery leasons has become clear in large registry trials. So far, the randomized controlled studies have shown the non-inferiority of PCI using DCB in comparison to DES in de novo leasons in small vessels. Also the non-inferiority of PCI using DCB in comparison to BMS was shown in the DEBUT trial in large vessels on patients at high bleeding risk. These results need to be confirmed in comparison of DCB to DES as the use of BMS is diminishing.
The hypothesis of the DEBATE trial is that the strategy using DCB and a shorter DAPT regimen is non-inferior to the treatment using DES and longer DAPT duration in the treatment of stable CAD or in ACS (UAP or NSTEMI) in patients on anticoagulation medication or otherwise on high bleeding risk. If non-inferiority is shown, the superiority of the DCB strategy over DES strategy will be tested.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 546
- Age ≥ 18 years
- Informed written consent
- At least one major or two minor bleeding risk criteria of Academic Research Consortium (ARC)
Major Criteria
- Long-term oral anticoagulation
- Severe or end stage chronic kidney disease (CKD) (estimated glomerular - filtration rate [eGFR] <30 ml/min)
- Hemoglobin <110 g/l
- Spontaneous bleeding requiring hospitalization and transfusion in the past 6 months
- Moderate to severe baseline thrombocytopenia (platelet count <100 x 10e9/L)
- Chronic bleeding diathesis
- Liver cirrhosis with portal hypertension
- Active cancer in the past 12 months
- Previous spontaneous ICH (at any time)
- Previous traumatic ICH within the past 12 months
- Presence of known brain arteriovenous malformation
- Moderate to severe ischemic stroke within the past 6 months
- Nondeferrable major surgery on dual antiplatelet therapy
- Recent major surgery or trauma within 30 days before PCI
Minor Criteria
- Age >75 years
- Moderate CKD (eGFR 30-59 ml/min)
- Hemoglobin 110-129 g/l for men and 110-119 g/l for women
- Spontaneous bleeding requiring hospitalization or transfusion within the past 12 - months not meeting major criterion
- Long term use of oral nonsteroidal antiinflammatory drugs or steroids
- Any ischemic stroke at any time not meeting major criterion
Either of the following:
- Stabile angina or dyspnea and a coronary narrowing causing myocardial ischemia detected in the angiogram. In stable patients prior PCI, the evidence of ischemia is needed acquired either by perfusion imaging or by pressure wire measurement (FFR) during coronary angiography unless the coronary stenosis is > 90% in diameter.
- ACS (UAP or NSTEMI): symptoms of heart ischemia≥ 20 minutes and ≥ 0,5mm ST-depression or transient ST-elevation or T-wave inversion at least in two adjacent leads and/or a high sensitivity troponin (hs-tnt) rise at least one unit above the 99. percentil or at least 50% rise in hs-tnt between two samples taken 1-3 hours apart.
At least one of the following:
- ≥1 de novo lesions in native coronary arteries or bypass vein grafts
- Reference diameter of the vessel is 2.0-5.0mm'
- Lesion length ≤ 40mm
- Lesion or lesions are suitable for PCI
- Inability to give written consent
- STEMI
- Reference diameter of the vessel is <2.0mm or >5.0 mm
- Bifurcation lesion requiring the stenting of either of the branches after predilatation (TIMI<3 or significant recoil >30% in the main epicardial vessel: LAD, LCX or RCA) after predilatation)
- Dissection affecting the flow (TIMI<3) or significant recoil (>30% in the main epicardial vessel: LAD, LCX or RCA) after predilatation
- in-stent restenosis
- Chronic total occlusion
- Life expectancy < 12 months
- Cardiogenic shock at the arrival to the coronary angiography
- Uncertainty about neurological recovery e.g. after resuscitation
- Need for bypass surgery by heart team decision
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Drug-coated balloon (DCB) Percutaneous coronary intervention using drug-coated balloon The coronary lesions fulfilling the inclusion criteria and randomized to the DCB group. Drug-eluting stent (DES) Percutaneous coronary intervention using drug-eluting stent The coronary lesions fulfilling the inclusion criteria and randomized to the DES group.
- Primary Outcome Measures
Name Time Method The composite of MACE and BARC type 2-5 bleeding episodes 12 months Major Adverse Cardiac Event = a composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia driven-target lesion revascularization (ID-TLR). BARC = Bleeding academic research consortium. In stable patients, the evidence of ischemia is acquired either by non-invasive testing (for example stress ECG or perfusion imaging) or by pressure wire measurement (FFR) during coronary angiography.
- Secondary Outcome Measures
Name Time Method The composite of MACE and BARC2-5 bleedings 24 and 36 months Major Adverse Cardiac Event = a composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia driven-target lesion revascularization (ID-TLR). BARC = Bleeding academic research consortium. In stable patients, the evidence of ischemia is acquired either by non-invasive testing (for example stress ECG or perfusion imaging) or by pressure wire measurement (FFR) during coronary angiography.
TLF 12, 24 and 36 months Target-lesion failure
The composite of TVF (Target-vessel failure) and BARC2-5 bleedings 12, 24 and 36 months Target-vessel failure. BARC = Bleeding academic research consortium.
The composite of TLF (Target-lesion failure) and BARC2-5 bleedings 12, 24 and 36 months Target-lesion failure. BARC = Bleeding academic research consortium.
The composite of TLR (Target-lesion revascularization) and BARC2-5 bleedings 12, 24 and 36 months Target-lesion revascularization. BARC = Bleeding academic research consortium.
Stroke (ischemic or hemorrhagic) or TIA 12, 24 and 36 months Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)
MACE 12, 24 and 36 months Composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia driven-target lesion revascularization (ID-TLR)
BARC2-5 bleedings 12, 24 and 36 months BARC = Bleeding academic research consortium
BARC3-5 bleedings 12, 24 and 36 months BARC = Bleeding academic research consortium
Total mortality 12, 24 and 36 months All-cause mortality
Cardiovascular mortality 12, 24 and 36 months Cardiovascular death is defined as death resulting from cardiovascular causes. The following categories may be collected:
1. Death caused by acute MI
2. Death caused by sudden cardiac, including unwitnessed, death
3. Death resulting from heart failure
4. Death caused by stroke
5. Death caused by cardiovascular procedures
6. Death resulting from cardiovascular hemorrhage
7. Death resulting from other cardiovascular causeTLR 12, 24 and 36 months Target-lesion revascularization
Myocardial infarction 12, 24 and 36 months Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)
TVF 12, 24 and 36 months Target-vessel failure
Acute vessel closure as defined by the international consensus criteria for definite/probable stent thrombosis 12, 24 and 36 months Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)
The composite of TLR (Target-lesion revascularization) and BARC3-5 bleedings 12, 24 and 36 months Target-lesion revascularization. BARC = Bleeding academic research consortium.
Hospitalization for urgent revascularization 12, 24 and 36 months Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)
Trial Locations
- Locations (14)
Central Hospital of Lapland
🇫🇮Rovaniemi, Lappi, Finland
Helsinki University Hospital
🇫🇮Helsinki, Uusimaa, Finland
Oulu university hospital
🇫🇮Oulu, Finland
Centre Hospitalier La Rochelle
🇫🇷La Rochelle, France
Tampere Heart Hospital
🇫🇮Tampere, Finland
University Hospital of Saarland
🇩🇪Homburg, Germany
University Hospital of Carl Gustav Carus
🇩🇪Dresden, Germany
Norfolk and Norwich University Hospital Nhs Foundation Trust
🇬🇧Norwich, United Kingdom
Kuopio University Hospital
🇫🇮Kuopio, Pohjois-Savo, Finland
Central Hospital of Päijät-Häme
🇫🇮Lahti, Finland
North Karelia Central Hospital
🇫🇮Joensuu, Finland
Central Hospital of Central Finland
🇫🇮Jyväskylä, Keski-Suomi, Finland
Turku University Hospital
🇫🇮Turku, Varsinais-Suomi, Finland
Satakunta Central Hospital
🇫🇮Pori, Finland