Bioresorbable Polymer ORSIRO Versus Durable Polymer RESOLUTE ONYX Stents (BIONYX)

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

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Angina Pectoris; Acute Coronary Syndrome; Unstable Angina Pectoris; Coronary Stenosis; Coronary Restenosis
• Intervention / Treatment: Device: Orsiro; Device: Resolute Onyx

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 2470
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Charleroi, Belgium
    • Chu Charleroi
  • Hasselt, Belgium
    • Jessa Ziekenhuis
• Israel
  • Haifa, Israel
    • Rambam
• Netherlands
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Emmen, Netherlands
    • TREANT Zorggroep
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Zuid Holland
    • Den Haag, Zuid Holland, Netherlands, 2504 LN
      • Haga ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Orsiro DES (Biotronik); 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; stents will be implanted in case of significant coronary artery disease; Other Names: Orsiro drug eluting stent
Active Comparator: RESOLUTE ONYX DES (Medtronic); 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; stents will be implanted in case of significant coronary artery disease based on coronary angiography; Other Names: Resolute Onyx drug eluting stent

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal stent deformation (LSD) and deliverability	Identification of deformation of a stent in the longitudinal axis during coronary angiographic assessment.	1 year

Collaborators and Investigators

• Sponsor: Thorax Centrum Twente
• Investigators: Principal Investigator: Clemens von Birgelen, MD, PhD, Thorax Centrum Twente

Publications and helpful links

General Publications

• von Birgelen C, Sen H, Lam MK, Danse PW, Jessurun GA, Hautvast RW, van Houwelingen GK, Schramm AR, Gin RM, Louwerenburg JW, de Man FH, Stoel MG, Lowik MM, Linssen GC, Said SA, Nienhuis MB, Verhorst PM, Basalus MW, Doggen CJ, Tandjung K. Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial. Lancet. 2014 Feb 1;383(9915):413-23. doi: 10.1016/S0140-6736(13)62037-1. Epub 2013 Oct 31. Erratum In: Lancet. 2014 Feb 1;383(9915):412.
• Sen H, Lam MK, Lowik MM, Danse PW, Jessurun GA, van Houwelingen KG, Anthonio RL, Tjon Joe Gin RM, Hautvast RW, Louwerenburg JH, de Man FH, Stoel MG, van der Heijden LC, Linssen GC, IJzerman MJ, Tandjung K, Doggen CJ, von Birgelen C. Clinical Events and Patient-Reported Chest Pain in All-Comers Treated With Resolute Integrity and Promus Element Stents: 2-Year Follow-Up of the DUTCH PEERS (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial (TWENTE II). JACC Cardiovasc Interv. 2015 Jun;8(7):889-99. doi: 10.1016/j.jcin.2015.01.033. Epub 2015 May 20.
• Pinxterhuis TH, Ploumen EH, Zocca P, Doggen CJM, Schotborgh CE, Anthonio RL, Roguin A, Danse PW, Benit E, Aminian A, Stoel MG, Linssen GCM, Geelkerken RH, von Birgelen C. Outcome after percutaneous coronary intervention with contemporary stents in patients with concomitant peripheral arterial disease: A patient-level pooled analysis of four randomized trials. Atherosclerosis. 2022 Aug;355:52-59. doi: 10.1016/j.atherosclerosis.2022.05.002. Epub 2022 May 20.
• Ploumen EH, Pinxterhuis TH, Zocca P, Roguin A, Anthonio RL, Schotborgh CE, Benit E, Aminian A, Danse PW, Doggen CJM, von Birgelen C, Kok MM. Impact of prediabetes and diabetes on 3-year outcome of patients treated with new-generation drug-eluting stents in two large-scale randomized clinical trials. Cardiovasc Diabetol. 2021 Oct 30;20(1):217. doi: 10.1186/s12933-021-01405-4.
• Ploumen EH, Buiten RA, Zocca P, Doggen CJ, Aminian A, Schotborgh CE, Jessurun GA, Roguin A, Danse PW, Benit E, von Birgelen C. First Report of 3-Year Clinical Outcome After Treatment With Novel Resolute Onyx Stents in the Randomized BIONYX Trial. Circ J. 2021 Oct 25;85(11):1983-1990. doi: 10.1253/circj.CJ-21-0292. Epub 2021 Jul 13.
• von Birgelen C, Zocca P, Buiten RA, Jessurun GAJ, Schotborgh CE, Roguin A, Danse PW, Benit E, Aminian A, van Houwelingen KG, Anthonio RL, Stoel MG, Somi S, Hartmann M, Linssen GCM, Doggen CJM, Kok MM. Thin composite wire strut, durable polymer-coated (Resolute Onyx) versus ultrathin cobalt-chromium strut, bioresorbable polymer-coated (Orsiro) drug-eluting stents in allcomers with coronary artery disease (BIONYX): an international, single-blind, randomised non-inferiority trial. Lancet. 2018 Oct 6;392(10154):1235-1245. doi: 10.1016/S0140-6736(18)32001-4. Epub 2018 Sep 22.
• van der Heijden LC, Kok MM, Zocca P, Jessurun GAJ, Schotborgh CE, Roguin A, Benit E, Aminian A, Danse PW, Lowik MM, Linssen GCM, van der Palen J, Doggen CJM, von Birgelen C. Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents (BIONYX): Rationale and design of the randomized TWENTE IV multicenter trial. Am Heart J. 2018 Apr;198:25-32. doi: 10.1016/j.ahj.2017.12.011. Epub 2017 Dec 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2016
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: July 23, 2015
• First Submitted That Met QC Criteria: July 24, 2015
• First Posted (Estimate): July 27, 2015

Study Record Updates

• Last Update Posted (Estimate): February 3, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Coronary Artery Disease; Acute Coronary Syndrome; Angina Pectoris; Angina, Unstable; Coronary Stenosis; Coronary Restenosis
• Other Study ID Numbers: P15-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No