Clinical trial NCT01781546: Drug-Eluting Balloon in Stable and Unstable Angina
Official title: Drug-Eluting Balloon in Stable and Unstable Angina: a Randomized Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: drug eluting balloon
bare metal stent
coronary artery disease
acute coronary syndrome
percutaneous coronary intervention
DEB
BMS
Lead sponsor: North Karelia Central Hospital
Sponsor class: OTHER
Collaborators: name: Kuopio University Hospital
name: University of Helsinki
name: Turku University Hospital
name: Central Hospital of Lapland, Finland
First posted: 2013-02-01
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare DEB with BMS in CAD patients who are at high risk of bleeding and in whom the use of DES is therefore avoided. Our hypothesis is that PCI with DEB is non-inferior to BMS in the treatment of stable CAD or in ACS (UAP or NSTEMI) in patients at high risk of bleeding.

Detailed description: Stenting has reduced the need of revascularization procedures in stable CAD and ACS as compared to POBA. The use of stents is favored in stable CAD and in ACS according the the present ESC guidelines. However, especially in patients on warfarin or in patients at a high bleeding risk, stenting (and the use of DES in particular) is not recommended because of the longer DAPT required. In these patients, BMS may be used to shorten the duration of DAPT. However, there are problems associated with the treatment using BMS. First of all, a considerable high rate of restenosis is associated with stenting with BMS. Furthermore, stenting may be complicated by the "no-reflow" phenomenon, a coronary dissection or the closure of side branch during the treatment of bifurcation lesions. Implantation of a stent also exposes the patient to stent thrombosis. In contrast, these problems may be avoided by the use of DEB with the provisional BMS strategy.

The use of DEB has already been established in the treatment of ISR. Despite the lack of data of RCTs, DEB is already widely used in a variety of clinical situations in which stenting is not desirable. These situations include for example anticoagulation treatment, a high bleeding risk, poor compliance regarding medication, small vessels, bifurcation lesions, long and/or calcified lesions, in case of a marked variation in the vessel reference caliber, in long lesions and in patients with ACS. The all-comer registry data is promising but only hypothesis generating. Thus, it would be very important and ethical to test the efficacy of DEB in a wider patient population in a randomized controlled study.

Our hypothesis is that DEB is non-inferior to BMS in the treatment of stable CAD or in ACS (UAP or NSTEMI) in patients on anticoagulation medication or otherwise having a high bleeding risk. Our study sheds light on the use of DEB in PCI of this challenging patient population. In most previous studies, BMS has been routinely added to the DEB treatment. This strategy seems not to yield any benefit but in contrast causes an increased risk of restenosis as compared to the DEB only strategy with provisional stenting. Finally, the current data on the use of DEB in patients with ACS is scarce and our study gives significant information also on this important issue.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Informed written consent
* At least one of the following

  1. Patient is using oral anticoagulation (warfarin, dabigatran or rivaroxaban)
  2. Anemia (hemoglobin below the threshold: \< 117g/l in women and \< 134 g/l in men) or thrombocytopenia (\<100) detected \<6 months prior the PCI
  3. Active malign disease (metastatic cancer or ongoing radio- or chemotherapy)
  4. Prior intracerebral hemorrhage or ischemic stroke
  5. Severe kidney or liver dysfunction (eGFR \< 30ml/kg/min, liver cirrhosis, BIL \>2x over threshold or ALAT \>3x over threshold)
  6. Elective surgery planned \< 12 months after the PCI
  7. General frailty for e.g. because of long corticosteroid treatment or generalized cachexia (BMI \< 20 kg/m2)
  8. Age ≥ 80 years
  9. Inability or suspected inability to use DAPT for 12 months
* Either of the following:

  10) Prior bleeding (BARC 2-5)
  1. Stable angina or dyspnea and a coronary narrowing causing myocardial ischemia detected in the angiogram. Ischemia is documented by the pressure wire measurement (FFR) or by a non-invasive test such as stress ECG test or perfusion imaging
  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. percentile or at least 50% rise in hs-tnt between two samples taken 3 hours apart
* ≥1 de novo lesions in native coronary arteries or bypass vein grafts
* Reference diameter of the vessel is 2,5-4,0mm
* Lesion or lesions are suitable for PCI

Exclusion Criteria:

* Inability to give written consent
* STEMI
* Reference diameter of the vessel is \<2,5mm or \>4,0mm
* Bifurcation lesion requiring the stenting of the side branch
* Dissection affecting the flow (TIMI\<3) or significant recoil (\>30% in main branch, \>50% in side branch) after predilatation
* In-stent restenosis
* Life expectancy \< 12 months
* Cardiogenic shock at the arrival to the coronary angiography
* Uncertainty about neurological recovery e.g. after resuscitation
* Unprotected left main (LM) lesion
* Chronic total occlusion (CTO)

Primary outcomes:
measure: MACE (Major Adverse Cardiac Event = a composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia driven target lesion revascularization (ID-TLR))
timeFrame: At 9 months
measure: ID-TLR (Ischemia Driven Target Lesion Revascularisation)
timeFrame: at 36 months
Secondary outcomes:
measure: ID-TLR (Ischemia Driven Target Lesion Revascularisation)
timeFrame: At 9 months
measure: Failure to treat the lesion
timeFrame: During PCI
Other outcomes:
measure: Control angiography and OCT imaging
timeFrame: At 6 months
measure: MACE (Major Adverse Cardiac Event = a composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia driven target lesion revascularization (ID-TLR))
timeFrame: at 36 months
measure: ID-TLR (Ischemia Driven Target Lesion Revascularisation)
timeFrame: at 36 months
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital Heart Center
city: Joensuu
country: Finland
facility: North Karelia Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: North Karelia Central Hospital
name: Tuomas Rissanen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: North Karelia Central Hospital
name: Antti Siljander, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rissanen TT, Uskela S, Eranen J, Mantyla P, Olli A, Romppanen H, Siljander A, Pietila M, Minkkinen MJ, Tervo J, Karkkainen JM; DEBUT trial investigators. Drug-coated balloon for treatment of de-novo coronary artery lesions in patients with high bleeding risk (DEBUT): a single-blind, randomised, non-inferiority trial. Lancet. 2019 Jul 20;394(10194):230-239. doi: 10.1016/S0140-6736(19)31126-2. Epub 2019 Jun 13.