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

Study Overview
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Brief Summary
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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.

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

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Medtronic Resolute Onyx Zotarolimus-Eluting Coronary Stent System
* Device: Biosensors BioFreedom BA9 Drug Coated Coronary Stent


Participation Criteria
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Eligibility Criteria
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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

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: Prospective, multi-center, blinded, randomized, controlled study enrolling eligible subjects at global centers. The enrollment period is anticipated to be approximately 14 months.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resolute Onyx stent<br>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<br>* Medtronic Resolute Onyx Zotarolimus-Eluting Coronary Stent System Treatment Followed by 1 month DAPT<br>|
| Active Comparator: BioFreedom stent<br>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<br>* Biosensors BioFreedom BA9 Drug Coated Coronary Stent Followed by 1 month DAPT<br>|

What is the study measuring?
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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 |