Clinical trial NCT04814212: Drug-Coated Balloon in Anticoagulated and Bleeding Risk Patients Undergoing PCI
Official title: Drug-Coated Balloon in Anticoagulated and Bleeding Risk Patients Undergoing PCI
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Keywords: drug-coated balloon
drug eluting stent
coronary artery disease
acute coronary syndrome
percutaneous coronary intervention
DCB
DES
drug coated balloon
drug-eluting stent
drug-eluting balloon
high bleeding risk
HBR
Lead sponsor: North Karelia Central Hospital
Sponsor class: OTHER
Collaborators: name: Central Hospital of Lapland
name: Kuopio University Hospital
name: Central Finland Hospital District
name: Helsinki University Central Hospital
name: Turku University Hospital
name: Oulu University Hospital
name: Tampere University Hospital
name: Satakunta Central Hospital
name: Päijät Häme Central Hospital
name: Norfolk and Norwich University Hospitals NHS Foundation Trust
name: Centre Hospitalier de La Rochelle
name: Hospital Universitario de Cabuenes
name: University Hospital Carl Gustav Carus
name: University Hospital, Saarland
First posted: 2021-03-24
Enrollment: 546
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled clinical trial
Primary purpose: TREATMENT

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.

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:

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

Primary outcomes:
measure: The composite of MACE and BARC type 2-5 bleeding episodes
timeFrame: 12 months
Secondary outcomes:
measure: The composite of MACE and BARC2-5 bleedings
timeFrame: 24 and 36 months
measure: MACE
timeFrame: 12, 24 and 36 months
measure: BARC2-5 bleedings
timeFrame: 12, 24 and 36 months
measure: BARC3-5 bleedings
timeFrame: 12, 24 and 36 months
measure: Total mortality
timeFrame: 12, 24 and 36 months
measure: Cardiovascular mortality
timeFrame: 12, 24 and 36 months
measure: TVF
timeFrame: 12, 24 and 36 months
measure: TLR
timeFrame: 12, 24 and 36 months
measure: TLF
timeFrame: 12, 24 and 36 months
measure: Myocardial infarction
timeFrame: 12, 24 and 36 months
measure: The composite of TVF (Target-vessel failure) and BARC2-5 bleedings
timeFrame: 12, 24 and 36 months
measure: The composite of TLF (Target-lesion failure) and BARC2-5 bleedings
timeFrame: 12, 24 and 36 months
measure: The composite of TLR (Target-lesion revascularization) and BARC2-5 bleedings
timeFrame: 12, 24 and 36 months
measure: The composite of TLR (Target-lesion revascularization) and BARC3-5 bleedings
timeFrame: 12, 24 and 36 months
measure: Acute vessel closure as defined by the international consensus criteria for definite/probable stent thrombosis
timeFrame: 12, 24 and 36 months
measure: Hospitalization for urgent revascularization
timeFrame: 12, 24 and 36 months
measure: Stroke (ischemic or hemorrhagic) or TIA
timeFrame: 12, 24 and 36 months
Other outcomes:
Locations:
city: Jyväskylä
country: Finland
facility: Central Hospital of Central Finland
state: Keski-Suomi
city: Rovaniemi
country: Finland
facility: Central Hospital of Lapland
state: Lappi
city: Kuopio
country: Finland
facility: Kuopio University Hospital
state: Pohjois-Savo
city: Helsinki
country: Finland
facility: Helsinki University Hospital
state: Uusimaa
city: Turku
country: Finland
facility: Turku University Hospital
state: Varsinais-Suomi
city: Joensuu
country: Finland
facility: North Karelia Central Hospital
city: Lahti
country: Finland
facility: Central Hospital of Päijät-Häme
city: Oulu
country: Finland
facility: Oulu university hospital
city: Pori
country: Finland
facility: Satakunta Central Hospital
city: Tampere
country: Finland
facility: Tampere Heart Hospital
city: La Rochelle
country: France
facility: Centre Hospitalier La Rochelle
city: Dresden
country: Germany
facility: University Hospital of Carl Gustav Carus
city: Homburg
country: Germany
facility: University Hospital of Saarland
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital Nhs Foundation Trust
Study officials:
affiliation: North Karelia Central Hospital
name: Tuomas T Rissanen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: