A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients (Onyx ONE)

Onyx ONE Study; A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients

The purpose of this study is to evaluate the clinical safety and effectiveness of the Resolute Onyx stent in subjects deemed at high risk for bleeding and/or medically unsuitable for more than 1 month DAPT treatment receiving reduced duration (1 month) of DAPT following stent implantation.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Medtronic Resolute Onyx Zotarolimus-Eluting Coronary Stent System; Device: Biosensors BioFreedom BA9 Drug Coated Coronary Stent

• Study Type: Interventional
• Enrollment (Actual): 2000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Bundaberg, Queensland, Australia, 4670
      • Bundaberg Cardiology - Friendly Society Private Hospital
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Adelaide Cardiology
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Saint Vincent's Hospital (Melbourne)
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Graz, Austria, 8036
    • LKH - Universitätsklinikum Graz
  • Innsbruck, Austria, 6020
    • A.ö. Landeskrankenhaus - Universitätskliniken Innsbruck
  • Wien, Austria, 1090
    • Allgemeines Krankenhaus - Universitätskliniken Wien
• Belgium
  • Charleroi, Belgium, 6042
    • C.H.U. de Charleroi
  • Leuven, Belgium, 3000
    • UZ Leuven - Campus Gasthuisberg
  • Liège, Belgium, 4000
    • CHU de Liège - Hôpital du Sart Tilman
• Bulgaria
  • Sofia, Bulgaria, 1700
    • Acibadem City Clinic
• France
  • Aix-en-Provence, France, 13097
    • Clinique Axium
  • Massy, France, 91300
    • Hôpital Privé Jacques Cartier
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Queen Elizabeth Hospital (Hong Kong)
• Ireland
  • Galway, Ireland
    • Galway University Hospitals - University Hospital Galway (UHG)
• Italy
  • Catania, Italy, 95124
    • Presidio Ospedaliero Ferrarotto Alessi
  • Milano, Italy, 20132
    • San Raffaele Scientific Institute
  • Milano, Italy, 20138
    • Centro Cardiologico Monzino
  • Roma, Italy, 00161
    • Umberto I - Policlinico di Roma
  • Bergamo
    • Seriate, Bergamo, Italy, 24068
      • Azienda Ospedaliera Bolognini Seriate - Ospedale Bolognini
• Korea, Republic of
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Medical Center
  • Gwangju, Korea, Republic of, 501-757
    • Chonnam National University Hospital
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 137-701
    • Seoul Saint Mary's Hospital
  • Wonju, Korea, Republic of, 220-701
    • Wonju Severance Christian Hospital
• Latvia
  • Riga, Latvia, 1002
    • Paula Stradiņa klīniskā universitates slimnīca
  • Riga, Latvia, LV-1079
    • Riga East University Hospital
• Lithuania
  • Kaunas, Lithuania, 50009
    • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Klinikos
• Malaysia
  • Kota Kinabalu, Malaysia, 94300
    • Sarawak Heart Centre
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara - National Heart Institute
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88300
      • Queen Elizabeth II Hospital
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak Heart Centre
  • Selangor Darul Ehsan
    • Kajang, Selangor Darul Ehsan, Malaysia, 43000
      • Hospital Serdang
• Netherlands
  • Den Haag, Netherlands, 2545 CH
    • HagaZiekenhuis - Locatie Leyweg
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum Heerlen
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum (MUMC)
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis
  • Venlo, Netherlands, 5912 BL
    • VieCuri Medisch Centrum voor Noord-Limburg - Locatie Venlo
  • Zwolle, Netherlands, 8025 AB
    • Isala Zwolle
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Hamilton, New Zealand
    • Waikato Hospital
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
  • Newtown, New Zealand, 6021
    • Wellington Hospital
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus-Ullevål Universitetssykehus
  • Stavanger, Norway, 4011
    • Stavanger Universitetssjukehus - Helse Stavanger HF
• Poland
  • Katowice, Poland, 40-635
    • Górnośląskie Centrum Medyczne im prof Leszka Gieca Śląskiego Uniwersytetu Medycznego w Katowicach
  • Lubin, Poland, 59-301
    • Miedziowe Centrum Zdrowia
  • Poznań, Poland, 61-848
    • Szpital Kliniczny Przemienienia Pańskiego
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
• Slovakia
  • Banska Bystrica, Slovakia, 97401
    • Stredoslovensky ustav srdcovych a cievnych chorob a.s
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08907
    • Hospital Universitari Bellvitge
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clínico Universitario Virgen de la Arrixaca
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias
• Sweden
  • Gävle, Sweden, 801 88
    • Gävle sjukhus
  • Stockholm, Sweden, 118 83
    • Södersjukhuset
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital in Solna
  • Västerås, Sweden, 721 89
    • Västmanlands sjukhus
  • Örebro, Sweden, 701 85
    • Universitetssjukhuset Örebro
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital - Universitätsspital Bern
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Cardiff and Vale University Health Board - University Hospital of wales (UHW)
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter NHS Foundation Trust
  • Glasgow, United Kingdom, G81 4HX
    • Golden Jubilee National Hospital - NHS Trust
  • London, United Kingdom, Nw3 2QG
    • Royal Free Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • The James Cook University Hospital - South Tees Hospitals NHS
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital
  • Portsmouth, United Kingdom, PO6 3LY
    • Queen Alexandra Hospital

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:

• Age ≥ 75 years old
• Any prior documented intracerebral bleed
• Any documented stroke in the last 12 months
• Hospital admission for bleeding during the prior 12 months
• Non-skin cancer diagnosed or treated ≤3 years
• Planned surgery within the next 12 months
• Renal failure defined as: Creatinine clearance <40 ml/min
• Thrombocytopenia (PLT <100,000/mm3)
• Severe chronic liver disease defined as: subjects who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy or jaundice

Exclusion Criteria:

• Pregnant and breastfeeding women
• Subjects requiring a planned PCI procedure after 1 month of index procedure
• Active bleeding at the time of inclusion
• Cardiogenic shock
• A known hypersensitivity or contraindication to aspirin, heparin and bivalirudin, P2Y12 inhibitors, mTOR inhibiting drugs such as zotarolimus, Biolimus A9 (or its derivatives), cobalt, nickel, platinum, iridium, chromium, molybdenum, polymer coatings (eg, BioLinx™), stainless steel (or other metal ions found in 316L stainless steel), zinc, or a sensitivity to contrast media, which cannot be adequately pre-medicated.
• PCI during the previous 6 months for a lesion other than the target lesion of the index procedure
• Participation in another clinical study within 12 months after index procedure
• Subjects with life expectancy of less than 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resolute Onyx stent; Subjects who fulfill the inclusion criteria and none of the exclusion criteria will be randomly allocated in a 1:1 fashion to treatment with a Resolute Onyx stent or the BioFreedom stent followed by 1-month DAPT. Subjects implanted with the Resolute Onyx stent will be assessed for non-inferiority compared to those implanted with the BioFreedom stent using a composite safety endpoint of cardiac death, myocardial infarction, and definite/probable stent thrombosis, at 1 year post-procedure.	Device: Medtronic Resolute Onyx Zotarolimus-Eluting Coronary Stent System; Medtronic Resolute Onyx Zotarolimus-Eluting Coronary Stent System Treatment Followed by 1 month DAPT
Active Comparator: BioFreedom stent; Subjects who fulfill the inclusion criteria and none of the exclusion criteria will be randomly allocated in a 1:1 fashion to treatment with a Resolute Onyx stent or the BioFreedom stent followed by 1-month DAPT. Subjects implanted with the Resolute Onyx stent will be assessed for non-inferiority compared to those implanted with the BioFreedom stent using a composite safety endpoint of cardiac death, myocardial infarction, and definite/probable stent thrombosis, at 1 year post-procedure.	Device: Biosensors BioFreedom BA9 Drug Coated Coronary Stent; Biosensors BioFreedom BA9 Drug Coated Coronary Stent Followed by 1 month DAPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint: Cardiac Death, Myocardial Infarction, or Stent Thrombosis	Powered for non-inferiority against BioFreedom (control), is a composite of cardiac death, myocardial infarction and definite/probable stent thrombosis. The combined clinical outcome of cardiac death, MI or stent thrombosis	1 year post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Lesion Failure	Defined as cardiac death, target vessel myocardial infarction (Q wave and non Q wave), or clinically driven target lesion revascularization(TLR) by percutaneous or surgical methods	2 year post-procedure
Procedure Success	Attainment of <30% residual stenosis by QCA (or <20% by visual assessment) AND TIMI flow 3 after the procedure, using any percutaneous method without the occurrence of MACE during the hospital stay.	2 year post-procedure
Cardiac Death	All deaths including cardiac death	2 year post- procedure
Major Cardiac Event	Major adverse cardiac event (MACE) defined as composite of death, myocardial infarction, or repeat target lesion revascularization (clinically driven) by percutaneous or surgical methods	2 year post- procedure
Myocardial Infarction	All myocardial infarction including Target Vessel Myocardial Infarction (TVMI)	2 year post-procedure
Target Vessel Failure	Target vessel failure (TVF) defined as composite of cardiac death, target vessel myocardial infarction, or clinically-driven target vessel revascularization (TVR) by percutaneous or surgical methods.	2 year post-procedure
Revascularization	All revascularizations (TLR, TVR and non-TVR)	2 year post-procedure
Stent Thrombosis	Stent thrombosis (per Academic Research Consortium (ARC) definition)	2 year post-procedure
Bleeding	Bleeding per BARC criteria	2 year post-procedure
Stroke	Stroke	2 year post-procedure
Lesion Success	The attainment of <30% residual stenosis by QCA (or < 20% by visual assessment) AND TIMI flow 3 after the procedure, using any percutaneous method	2 year post-procedure
Device success	Attainment of <30% residual stenosis by QCA (or <20% by visual assessment) AND TIMI flow 3 after the procedure, using the assigned device only.	2 year post-procedure

Collaborators and Investigators

• Sponsor: Medtronic Vascular
• Investigators: Principal Investigator: Stephan Windecker, MD, Bern University Hospital, Bern, Switzerland; Principal Investigator: Azeem Latib, MD, San Raffaele Scientific Institute, Milan, Italy; Principal Investigator: Elvin Kedhi, MD, Isala Zwolle, Netherlands

Publications and helpful links

General Publications

• Windecker S, Latib A, Kedhi E, Kirtane AJ, Kandzari DE, Mehran R, Price MJ, Abizaid A, Simon DI, Worthley SG, Zaman A, Hudec M, Poliacikova P, Kahar Bin Abdul Ghapar A, Selvaraj K, Petrov I, Mylotte D, Pinar E, Moreno R, Fabbiocchi F, Pasupati S, Kim HS, Aminian A, Tie C, Wlodarczak A, Hur SH, Marx SO, Ali ZA, Parke M, Lung TH, Stone GW; Onyx ONE Investigators. Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Final 2-Year Results From Onyx ONE. JACC Cardiovasc Interv. 2022 Jun 13;15(11):1153-1163. doi: 10.1016/j.jcin.2022.04.010.
• Windecker S, Latib A, Kedhi E, Kirtane AJ, Kandzari DE, Mehran R, Price MJ, Abizaid A, Simon DI, Worthley SG, Zaman A, Hudec M, Poliacikova P, Abdul Ghapar AKB, Selvaraj K, Petrov I, Mylotte D, Pinar E, Moreno R, Fabbiocchi F, Pasupati S, Kim HS, Aminian A, Tie C, Wlodarczak A, Hur SH, Marx SO, Jankovic I, Brar S, Bousquette L, Liu M, Stone GW; ONYX ONE Investigators. Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk. N Engl J Med. 2020 Mar 26;382(13):1208-1218. doi: 10.1056/NEJMoa1910021. Epub 2020 Feb 12.
• Kedhi E, Latib A, Abizaid A, Kandzari D, Kirtane AJ, Mehran R, Price MJ, Simon D, Worthley S, Zaman A, Brar S, Liu M, Stone GW, Windecker S. Rationale and design of the Onyx ONE global randomized trial: A randomized controlled trial of high-bleeding risk patients after stent placement with 1 month of dual antiplatelet therapy. Am Heart J. 2019 Aug;214:134-141. doi: 10.1016/j.ahj.2019.04.017. Epub 2019 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2017
• Primary Completion (Actual): September 27, 2018
• Study Completion (Actual): October 9, 2020

Study Registration Dates

• First Submitted: October 20, 2017
• First Submitted That Met QC Criteria: November 13, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: MDT17054RES007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No