Drug-eluting Balloon Versus Drug-eluting Stent for High Bleeding Risk Angioplasty

Study Overview
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Brief Summary
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Randomized, single-blind, single-center, non-inferiority clinical trial to compare target lesion failure (TLF) at 12 months in high bleeding risk patients undergoing elective coronary percutaneous intervention comparing limus-eluting balloon vs. limus-eluting stents.

Detailed Description
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Drug Eluting Stents (DES) are the devices of choice for coronary angioplasty, including in patients with high-bleeding risk. Different studies have been done to determine which strategy improves bleeding outcomes without risking the benefit of stenting. Different Double Anti-Platelet Therapy (DAPT) durations in different devices have shown that it is safe to reduce DAPT, with an increase in ischemic events but a better net clinical outcome. Safety and efficacy of Drug Eluting Balloons (DEB) were proved when it was compared with Bare Metal Stents (BMS) in de-novo coronary lesions by presenting no events of target vessel closure after treatment. Our hypothesis is that treating this group of high-bleeding risk patients with DEB will be no-inferior in terms of target vessel failure at 12 months when compared with DES for treatment of de-novo coronary lesions in high bleeding risk population, reducing incidence of significant bleeding events with DAPT reduction.

Official Title
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Drug-Eluting Balloon Versus Drug-eluting Stent On de Novo coRonary Artery Disease in Patients With High Bleeding Risk

Conditions
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High Bleeding Risk, Coronary Artery Disease (CAD), Percutaneous Coronary Intervention (PCI)

Intervention / Treatment
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* Device: Drug Eluting Balloon (DEB)
* Device: Drug Eluting Stents (DES)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years old or older with an ischemic de-novo lesion(s) in a 2.5 - 4.0 mm reference diameter coronary artery suitable for elective percutaneous coronary intervention, in context of acute coronary syndrome or chronic coronary syndrome with evidence of ischemia by non-invasive study or pressure guidewire that can be treated by DEB or DES, and has at least 1 major or 2 minor Academic Research Consortium High Bleeding Risk criteria: Major criteria: Anticipated use of long-term oral anticoagulation Severe or end-stage CKD (eGFR <30 mL/min) Hemoglobin < 11 g/dL Spontaneous bleeding requiring hospitalization or transfusion in the last 6 months, or any time, if recurrent. Moderate or severe baseline thrombocytopenia (<100,000/uL) Chronic bleeding diathesis Liver cirrhosis with portal hypertension Active malignancy (excluding nonmelanoma skin cancer) within the past 12 months Previous spontaneous intracranial hemorrhage Previous traumatic intracranial hemorrhage within the past 12 months Presence of Brain arteriovenous malformation (AVM) Moderate or severe ischemic stroke (NIHSS score equal or more than 5) within the past 6 months Non deferrable major surgery while on DAPT Recent major surgery or major trauma within 30 days before PCI Minor Criteria: Age 75 years old and older Moderate Chronic Kidney Disease (CKD) (eGFR 30-59 mL/min) Hemoglobin 11 - 12.9 g/dL in men and 11 - 11.9 g/dL in women Spontaneous bleeding requiring hospitalization or transfusion within the past 12 months, not meeting major criterion Long term use of NSAIDs or steroids Any ischemic stroke at any time not meeting major criterion Exclusion Criteria: STEMI undergoing primary PCI Any ACS undergoing urgent PCI Cardiogenic shock or resuscitation with uncertain neurological status at arrival to PCI Unprotected left main lesion Life expectancy < 12 months Reference vessel diameter < 2.5 mm or > 4.0 mm Bifurcation lesion requiring 2-stent technique Chronic total occlusion In-stent restenosis Dissection affecting the flow (TIMI<3) or significant recoil (>30% in main branch, >50% in side branch) after predilatation Inability to give written consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, single-blind, non-inferiority clinical trial enrolling high bleeding risk patients and coronary artery disease to be treated by percutaneous coronary intervention at the National Institute of Cardiology Ignacio Chávez in México. Included patients will have follow-up at the outpatient clinic through 1 year, until death or study exit, whichever comes first.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug Eluting Balloon (DEB)<br>High Bleeding Risk patients treated with 2.5 - 4.0 mm drug-eluting balloons (DEB). Bailout stenting is permitted in case of a flow-limiting dissection or significant recoil (>30% in main branch and >50% side-branch), includes both stable coronary artery disease (SCAD) and acute coronary syndromes (ACS) patients undergoing elective Percutaneous Coronary Intervention (PCI). | Device: Drug Eluting Balloon (DEB)<br>* Size (diameter and length) will be chosen at operator's discretion aid by simple angiography, quantitative coronary analysis (QCA), or intravascular image; so that the lesion previously prepared and 2 mm at each end are covered by DEB, and the diameter and pressure used aims a balloon to artery ratio of 1. In case of significant recoil (more than 30% for main vessels and 50% for side vessels), coronary perforation or flow limiting dissection, provisional stent will be implanted with a stent to artery ratio of 1.1 with stent post-dilatation when indicated. Device will be used in accordance with the CE mark instructions. DAPT will be given for a month with aspirin and a P2Y12 inhibitor (clopidogrel will be favored). Single anti-platelet therapy (SAPT) with aspirin will be continued thereafter.<br>* Other names: MagicTouch, Sirolimus coated balloon catheter, diameters 2.5 - 4.0 mm (Concept Medicals, Surat, India);|
| Active Comparator: Drug Eluting Stents (DES)<br>High Bleeding Risk patients treated with 2.5 - 4.0 mm drug-eluting stents (DES). Includes both stable CAD and ACS patients undergoing elective PCI. | Device: Drug Eluting Stents (DES)<br>* Size (diameter and length) will be chosen at operator's discretion aid by simple angiography, quantitative coronary analysis (QCA), or intravascular image; so that the lesion previously prepared and 2 mm at each end are covered by DES with an stent to artery ratio of 1.1. Post-dilatation will be performed when indicated. Devices will be used in accordance with the CE mark instructions. DAPT will be indicated according to actual international guidelines.<br>* Other names: Synergy, Everolimus eluting stent, diameters 2.5 - 4.0 mm (Boston Scientific, Natick, MA, USA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Lesion Failure (TLF) | Composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target lesion revascularization | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death | Rate of death resulting from cardiovascular causes in each group: 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 Any MI not clearly attributable to a non-target vessel will be considered as target-vessel MI. Percutaneous coronary intervention (PCI) related MI is termed type 4a MI. | 12 months | 
| Myocardial Infarction related to the treated vessel | Rate of myocardial infarction related to the treated vessel (according to the 4th international definition of myocardial infarction) in each group: detection of an increase or decrease in cardiac troponin values with at least 1 of the values above the upper reference limit of the 99th percentile and at least 1 of the following conditions : Symptoms of acute myocardial ischemia. New ischemic changes in the electrocardiogram. Appearance of pathological Q waves. Imaging evidence of loss of viable myocardium or new regional abnormalities in myocardial wall mobility following a pattern compatible with ischemic etiology. Identification of a coronary thrombus by angiography with intracoronary imaging or by autopsy Any MI that cannot be clearly attributed to a vessel other than the revascularized one will be considered as MI related to the treated vessel. | 12 months | 
| Target Lesion Revascularization | Rate of repeated percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion | 12 months | 
| Target Vessel Failure (TVF) | Rate of TVF in each group (composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target vessel revascularization) | 12 months | 
| Target Vessel Revascularization | Rate of repeated percutaneous intervention or surgical bypass of any segment of the target vessel in each group. | 12 months | 
| Non-cardiovascular death | Rate of any death that is not thought to be the result of a cardiovascular cause in each group: Death resulting from malignancy Death resulting from pulmonary causes Death caused by infection (includes sepsis) Death resulting from gastrointestinal causes Death resulting from accident/trauma Death caused by other noncardiovascular organ failure Death resulting from other noncardiovascular cause | 12 months | 
| Major Bleeding | Incidence of bleeding complications according to The Bleeding Academic Research Consortium 2 (BARC-2) scale: 3 or greater | 12 months | 
| Technical success | Rate of restoration of antegrade Thrombolysis In Myocardial Infarction (TIMI) flow 2 or 3 and a <30% residual stenosis. | Periprocedural | 
| Subgroup analysis of target lesion failure | Rate of TLF in treatment of bifurcations vs no bifurcation, by vessel size, in diabetes, by clinical Presentation (acute or chronic). | 12 months | 
| Subgroup analysis of major bleeding events | Rate of BARC 3-5 bleeding events in patients with anticoagulation vs no anticoagulation, by DAPT duration, by inclusion criteria | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Eluting Balloon (DEB), Drug Eluting Stent (DES), High bleeding risk (HBR), High hemorrhagic risk, Dual anti-platelet therapy (DAPT)