Drug-Coated Balloon in Anticoagulated and Bleeding Risk Patients Undergoing PCI

Overview

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.

Interventions

• Device Percutaneous coronary intervention using drug-coated balloon
  SeQuent Please (BBraun) + tailored antithrombotic regimen: 1. Stable patients without OAC: perioperative SAPT (preferably) or perioperative DAPT followed by lifelong SAPT 2. Stable patients with OAC: perioperative SAPT (preferably) or perioperative DAPT and lifelong OAC 3. ACS patients without OAC: 1-month DAPT followed by lifelong SAPT 4. ACS patients with OAC: perioperative DAPT followed by 1-month SAPT and lifelong OAC
• Device Percutaneous coronary intervention using drug-eluting stent
  Biofreedom (Biosensors), Synergy (Boston Scientific), Ultimaster Tansei (Terumo) and Integrity Onyx (Medtronic), Xience Pro S (Abbott) or Promus Elite (Boston Scientific) or any other DES can also be used provided that it has a CE mark for 1-month DAPT, combined with tailored antithrombotic regimen: 1. Stable patients without OAC: 1-month DAPT followed by lifelong SAPT 2. Stable patients with OAC: perioperative DAPT followed by 6 months SAPT (ADP receptor blocker) and life-long OAC 3. ACS patie

Primary outcome measures

• The composite of MACE and BARC type 2-5 bleeding episodes [Time frame: 12 months]

Secondary outcome measures (12)

• The composite of MACE and BARC2-5 bleedings [Time frame: 24 and 36 months]
• MACE [Time frame: 12, 24 and 36 months]
• BARC2-5 bleedings [Time frame: 12, 24 and 36 months]
• BARC3-5 bleedings [Time frame: 12, 24 and 36 months]
• Total mortality [Time frame: 12, 24 and 36 months]
• Cardiovascular mortality [Time frame: 12, 24 and 36 months]
• TVF [Time frame: 12, 24 and 36 months]
• TLR [Time frame: 12, 24 and 36 months]
• TLF [Time frame: 12, 24 and 36 months]
• Myocardial infarction [Time frame: 12, 24 and 36 months]
• The composite of TVF (Target-vessel failure) and BARC2-5 bleedings [Time frame: 12, 24 and 36 months]
• The composite of TLF (Target-lesion failure) and BARC2-5 bleedings [Time frame: 12, 24 and 36 months]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Finland · 10 centers

• Central Hospital of Central Finland — Jyväskylä
• Central Hospital of Lapland — Rovaniemi
• Kuopio University Hospital — Kuopio
• Turku University Hospital — Turku
• Helsinki University Hospital — Helsinki
• North Karelia Central Hospital — Joensuu
• Central Hospital of Päijät-Häme — Lahti
• Oulu university hospital — Oulu
• … and 2 more centers

Germany · 2 centers

• University Hospital of Carl Gustav Carus — Dresden
• University Hospital of Saarland — Homburg

France · 1 center

• Centre Hospitalier La Rochelle — La Rochelle

United Kingdom · 1 center

• Norfolk and Norwich University Hospital Nhs Foundation Trust — Norwich

Identifiers

NCT: NCT04814212 · DEBATE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗