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

Coronary Artery Disease Clinical Trial

— DEBATE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04814212
• Other study ID #: DEBATE
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: January 1, 2028

Study information

• Verified date: November 2023
• Source: North Karelia Central Hospital
• Contact: Tuomas Rissanen, MD, PhD
• Phone: +358505998022
• Email: tuomas.rissanen[@]siunsote.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 546
• Est. completion date: January 1, 2028
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. 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.

2. 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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Hemorrhage
• Myocardial Ischemia

Intervention

Device:
• Percutaneous coronary intervention using drug-coated balloon
SeQuent Please (BBraun) + tailored antithrombotic regimen: Stable patients without OAC: perioperative SAPT (preferably) or perioperative DAPT followed by lifelong SAPT Stable patients with OAC: perioperative SAPT (preferably) or perioperative DAPT and lifelong OAC ACS patients without OAC: 1-month DAPT followed by lifelong SAPT ACS patients with OAC: perioperative DAPT followed by 1-month SAPT and lifelong OAC
• 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: Stable patients without OAC: 1-month DAPT followed by lifelong SAPT Stable patients with OAC: perioperative DAPT followed by 6 months SAPT (ADP receptor blocker) and life-long OAC ACS patients without OAC: 3-month DAPT followed by lifelong SAPT ACS patients with OAC: perioperative DAPT followed by 6 months SAPT (ADP receptor blocker) and lifelong OAC

Locations

Country	Name	City	State
Finland	Helsinki University Hospital	Helsinki	Uusimaa
Finland	North Karelia Central Hospital	Joensuu
Finland	Central Hospital of Central Finland	Jyväskylä	Keski-Suomi
Finland	Kuopio University Hospital	Kuopio	Pohjois-Savo
Finland	Central Hospital of Päijät-Häme	Lahti
Finland	Oulu university hospital	Oulu
Finland	Satakunta Central Hospital	Pori
Finland	Central Hospital of Lapland	Rovaniemi	Lappi
Finland	Tampere Heart Hospital	Tampere
Finland	Turku University Hospital	Turku	Varsinais-Suomi
France	Centre Hospitalier La Rochelle	La Rochelle
Germany	University Hospital of Carl Gustav Carus	Dresden
Germany	University Hospital of Saarland	Homburg
United Kingdom	Norfolk and Norwich University Hospital Nhs Foundation Trust	Norwich

Sponsors (15)

Lead Sponsor

Collaborator

North Karelia Central Hospital

Central Finland Hospital District, Central Hospital of Lapland, Centre Hospitalier de La Rochelle, Helsinki University Central Hospital, Hospital Universitario de Cabuenes, Kuopio University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust, Oulu University Hospital, Päijät Häme Central Hospital, Satakunta Central Hospital, Tampere University Hospital, Turku University Hospital, University Hospital Carl Gustav Carus, University Hospital, Saarland

Countries where clinical trial is conducted

Finland,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The composite of MACE and BARC type 2-5 bleeding episodes	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.	12 months
Secondary	The composite of MACE and BARC2-5 bleedings	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.	24 and 36 months
Secondary	MACE	Composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia driven-target lesion revascularization (ID-TLR)	12, 24 and 36 months
Secondary	BARC2-5 bleedings	BARC = Bleeding academic research consortium	12, 24 and 36 months
Secondary	BARC3-5 bleedings	BARC = Bleeding academic research consortium	12, 24 and 36 months
Secondary	Total mortality	All-cause mortality	12, 24 and 36 months
Secondary	Cardiovascular mortality	Cardiovascular death is defined as death resulting from cardiovascular causes. The following categories may be collected: Death caused by acute MI; Death caused by sudden cardiac, including unwitnessed, death; Death resulting from heart failure; Death caused by stroke; Death caused by cardiovascular procedures; Death resulting from cardiovascular hemorrhage; Death resulting from other cardiovascular cause	12, 24 and 36 months
Secondary	TVF	Target-vessel failure	12, 24 and 36 months
Secondary	TLR	Target-lesion revascularization	12, 24 and 36 months
Secondary	TLF	Target-lesion failure	12, 24 and 36 months
Secondary	Myocardial infarction	Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)	12, 24 and 36 months
Secondary	The composite of TVF (Target-vessel failure) and BARC2-5 bleedings	Target-vessel failure. BARC = Bleeding academic research consortium.	12, 24 and 36 months
Secondary	The composite of TLF (Target-lesion failure) and BARC2-5 bleedings	Target-lesion failure. BARC = Bleeding academic research consortium.	12, 24 and 36 months
Secondary	The composite of TLR (Target-lesion revascularization) and BARC2-5 bleedings	Target-lesion revascularization. BARC = Bleeding academic research consortium.	12, 24 and 36 months
Secondary	The composite of TLR (Target-lesion revascularization) and BARC3-5 bleedings	Target-lesion revascularization. BARC = Bleeding academic research consortium.	12, 24 and 36 months
Secondary	Acute vessel closure as defined by the international consensus criteria for definite/probable stent thrombosis	Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)	12, 24 and 36 months
Secondary	Hospitalization for urgent revascularization	Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)	12, 24 and 36 months
Secondary	Stroke (ischemic or hemorrhagic) or TIA	Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document will be used (Circulation. 2018;137:2635-2650)	12, 24 and 36 months