Bioresorbable Polymer ORSIRO Versus Durable Polymer RESOLUTE ONYX Stents

Study Overview
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Brief Summary
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The introduction of drug-eluting stents (DES) in the treatment of coronary artery disease has led to a significant reduction in morbidity. However, the first generation of these devices had no positive impact on the mortality after PCI (compared to bare metal stents), which was greatly attributed to a somewhat increased incidence of late and very late stent thrombosis. Concerns about the role of durable polymers as a potential trigger of inflammation and finally adverse events also led to the development of DES with bioresorbable coatings, which leave after degradation of the coating only a bare metal stent in the vessel wall that does not induce an inflammatory response. While such bioresorbable polymer DES are increasingly used in clinical practice, data from head-to-head comparisons between bioresorbable polymer DES with a contemporary highly flexible new generation permanent polymer coated DES.

Detailed Description
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rationale: The introduction of drug-eluting stents (DES) in the treatment of coronary artery disease has led to a significant reduction in morbidity. However, the first generation of these devices had no positive impact on the mortality after PCI (compared to bare metal stents), which was greatly attributed to a somewhat increased incidence of late and very late stent thrombosis. Concerns about the role of durable polymers as a potential trigger of inflammation and finally adverse events also led to the development of DES with bioresorbable coatings, which leave after degradation of the coating only a bare metal stent in the vessel wall that does not induce an inflammatory response. While such bioresorbable polymer DES are increasingly used in clinical practice, data from head-to-head comparisons between bioresorbable polymer DES with a contemporary highly flexible new generation permanent polymer coated DES. Aim: The aim of the study is to compare the outcome of the bioresorbable polymer coated stent (ORSIRO) and a new generation permanent polymer coated stent (RESOLUTE ONYX) in an all-comers patient population and non-inferiority setting. Study design: The study is a prospective, randomized, single-blinded, multicentre trial with 1:1 randomization for drug-eluting stent type, stratified for gender and the presence of diabetes mellitus. Study population: Patients who require percutaneous coronary intervention (PCI) for the treatment of coronary stenoses with an indication for DES use, according to current guidelines and/or the operators clinical judgement. All clinical syndromes will be included. A total of 2,470 patients will be included. Intervention: One group will receive the ORSIRO stent, the other group will receive the RESOLUTE ONYX stent. All other intervention and procedural characteristics are similar. Primary study outcome: Incidence of target vessel failure (TVF) at 1 year follow-up (according to ARC definitions). Components of the primary endpoint in hierarchical order: - Cardiac death: all deaths are considered cardiac, unless an unequivocal non-cardiac cause can be established. - Target vessel related myocardial infarction (MI) that is Q-wave or non-Q-wave, that can be related to the target vessel or cannot be related to another vessel. - Clinically driven repeated target vessel revascularization by means of PCI or coronary artery bypass grafting (CABG).

Official Title
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Bioresorbable Polymer ORSIRO Versus Durable Polymer RESOLUTE ONYX Stents (BIONYX): A Randomized Trial With Stent Evaluation in All-comers IV (TWENTE IV)

Conditions
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Coronary Artery Disease, Angina Pectoris, Unstable Angina Pectoris, Acute Coronary Syndrome, Coronary Stenosis, Coronary Restenosis

Intervention / Treatment
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* Device: Orsiro
* Device: Resolute Onyx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of 18 years and older, requiring PCI for the treatment of significant coronary artery or bypass graft lesions, being eligible for treatment with drug eluting stents according to clinical guidelines and/or the operators' judgement, and capable of providing informed consent. Patients with all clinical syndromes will be enrolled without any exclusion based on number, type, location or length of lesions to be treated. Exclusion Criteria: Known intolerance to components of one of the study DES, or known intolerance to antithrombotic and/or anticoagulant therapy that prevents adherence to any dual anti-platelet therapy (DAPT). Planned elective surgical procedure necessitating interruption of DAPT during the first 3 months after randomization. Participation in another randomized cardiovascular device trial or randomized pharmacological study related to antithrombotic and/or anticoagulant therapy before reaching the primary endpoint. Known pregnancy, adherence to scheduled follow-up is unlikely, or life expectancy is assumed to be less than 1 year

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Orsiro DES (Biotronik)<br>The ORSIRO hybrid coating DES (Biotronik, Switzerland) is a device which includes a modern, highly flexible, thin-strut stent platform, eluting sirolimus from a thin biodegradable BIO-lute coating grom PLLA (poly(L-lactic acid)) which is located mainly on the abluminal side. | Device: Orsiro<br>* stents will be implanted in case of significant coronary artery disease<br>* Other names: Orsiro drug eluting stent;|
| Active Comparator: RESOLUTE ONYX DES (Medtronic)<br>The RESOLUTE ONYX is a permanent polymer DES that uses a novel highly flexible metallic stent backbone with increased radiographic visibility eluting the drug zotarolimus from the BioLinx durable polymer coating. The stent platform uses corewire technology that allows the stent to have a denser core metal surrounded by outer layer of cobalt-chromium. | Device: Resolute Onyx<br>* stents will be implanted in case of significant coronary artery disease based on coronary angiography<br>* Other names: Resolute Onyx drug eluting stent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target vessel failure (TVF) | Composite endpoint consisting of: Cardiac death (All deaths are considered cardiac, unless an unequivocal non-cardiac cause can be established); Target vessel related MI (Q-wave or non-Q-wave myocardial infarction that can be related to the target vessel or cannot be related to another vessel); Clinically driven repeated target vessel revascularization by means of CABG or PCI. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death at 1 and 2 year follow-up | Death distinguished into: cardiac, vascular, other causes, all-cause mortality | 1 and 2 year | 
| Myocardial infarction at 1 and 2 year follow-up | Myocardial infarction distinguished into Q-wave and non-Q-wave myocardial infarction | 1 and 2 year | 
| Revascularization at 1 and 2 year follow-up | Target-vessel revascularization distinguished into PCI or CABG | 1 and 2 year | 
| Stent thrombosis at 1 and 2 year follow-up | Stent thrombosis was distinguished into definite, probable and possible according to the Academic Research Consortium (ARC) definition. | 1 and 2 year | 
| Target lesion failure (TLF) at 1 and 2 year follow-up | Composite endpoint consisting of : cardiac death; target vessel-related MI; clinically driven target lesion revascularization (TLR) | 1 and 2 year | 
| Major adverse cardiac events (MACE) at 1 and 2 year follow-up | Composite endpoint consisting of: any death; any myocardial infarction emergent CABG; clinically indicated TLR | 1 and 2 year follow-up | 
| Patient oriented composite endpoint (POCE) at 1 and 2 year follow-up | Composite endpoint consisting of: any death; any myocardial infarction; any revascularization. | 1 and 2 year follow-up | 
| Major Bleeding at 1 and 2 year follow-up | Major bleeding that require surgery or blood transfusions or cerebral hemorrhages | 1 and 2 year follow-up |