BIOFLOW-Dual Anti-Platelet Therapy

Study Overview
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Brief Summary
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BIOFLOW-DAPT is a prospective, multi-center, international, two-arm randomised controlled clinical study. A total of 1,948 subjects will be randomised 1:1 to receive either Orsiro or Resolute onyx. After index procedure, all patients will receive DAPT (ASA + P2Y12 inhibitor) for 30 days, followed by monotherapy with either P2Y12 inhibitor or ASA only until the end of the study.

Official Title
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BIOTRONIK- A Prospective, Randomised, Multi-center Study to Assess the Safety of the Orsiro Mission Stent Compared to Resolute Onyx Stent in Subjects at High Risk of Bleeding in Combination With 1-month Dual Antiplatelet Therapy (DAPT)

Conditions
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Percutaneous Intervention

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is acceptable candidate for treatment with a DES Subject is considered at high bleeding risk (HBR), defined as meeting one or more of the following criteria at the time of enrollment: >=75 years of age Moderate (estimated GFR 30-59ml/min) or severe (estimated GFR <= 30ml/min) chronic kidney disease or failure (dialysis dependent) Advanced liver disease, defined as having cirrhosis with or without portal hypertension and with or without gastroesophageal varices Cancer (excluding non-melanoma skin cancer) diagnosed or treated within the previous 12 months or actively treated Anemia with haemoglobin < 11.0 g/dL or requiring transfusion within 4 weeks prior to randomisation baseline thrombocytopenia defined as a platelet count < 100,000/mm3. History of stroke (ischemic or haemorrhagic), previous intracerebral hemorrhage (ICH) (spontaneous at any time or traumatic within the past 12 months) or presence of a brain arteriovenus malformation history of hospitalisation for bleeding within the past 12 months Chronic clinically significant bleeding diathesis Clinical indication for chronic or lifelong oral anticoagulation (OAC) (with a vitamin K antagonist or non-vitamin K OAC) clinically indication for chronic or lifelong steroid or oral non-steroidal anti-inflammation drug(s) (NSAIDs), other than aspirin Nondeferrable major surgery on DAPT Recent major surgery or trauma within 30 days before PCI PRECISE DAPT score >= 25 Subject is >=18 years or the minimum age required for legal adult consent in the country of enrollment Subject is capable ( no legally authorised representative allowed) to provide written informed consent as approved by the Institutional Review Board (IRB)/ Ethics Committee (EC) of the respective clinical site prior to any study related procedure. Subject is willing to comply with all protocol and follow-up requirements, including agreement to discontinue DAPT at 1 month. Subject is eligible for dual antiplatelet therapy treatment with aspiring plus a P2Y12 inhibitor agent for 1-month post index procedure Exclusion Criteria: Subject who previously experienced a stent or scaffold thrombosis in any coronary vessel Subject has a known allergy to all types of P2Y12 inhibitor (Clopidogrel, Ticagrelor, Prasugrel, Ticlopidine and Cangrelor; thus preventing the use of the appropriate P2Y12 inhibitor), aspirin, both heparin and bivalirudin, L-605 cobalt-chromium (Co-Cr) alloy or one of its major elements (cobalt, chromium, tungsten, nickel, molybdenum, platinum and iridium, silicon carbide, PLLA, polymers, mTOR inhibiting drugs such as zotarolimus or sirolimus, or contrast media Revascularisation of any target vessel within 9 months prior to the index procedure Subject with documented left ventricular ejaculation fraction (LVEF) < 30% as evaluated by the most recent imaging exam (i.e. echocardiogram, ventriculogram, MUGA, etc.), but within 90 days pre/procedure or during the index procedure. Subject judged by physician as inappropriate for discontinuation from DAPT at 1 month following index procedure, due to another condition requiring chronic DAPT Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor and/or aspirin within the first month post-index procedure. Note - planned staged procedure at the time of index procedure is not allowed Active bleeding at the time of inclusion Subject with a current medical condition with a life expectancy of less than 12 months Subject is currently participating or intends to participate in another investigational drug or device trial within 12 months following index procedure or any other clinical trial that may interfere with the treatment or protocol of this study Subject is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study In the investigator' opinion, subject will not be able to comply with the follow-up requirements Subjects who needs an impartial witness to give an informed consent

Ages Eligible for Study
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Minimum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orsiro<br> | Device: Orsiro Mission<br>* Percutaneous intervention using Orsiro Mission stent<br>|
| Active Comparator: Resolute Onyx<br> | Device: Resolute Onyx<br>* Percutaneous intervention using Resolute Onyx stent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Major Adverse Cardiovascular Event (MACE) 12 months post-operation | The composite of cardiac death, myocardiac infraction (MI) and definite or probable stent thrombosis at 12 months post-index procedure | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of stent thrombosis (ST) | Rate of definite/ possible ST utilizing the Academic Research Consortium-2 (ARC-2) definition | 12 months | 
| Rate of Major Adverse Cerebral &Cardiovascular Event (MACCE) | Rate of the composite of all-cause death, MI, and stroke | 12 months | 
| Death rate | Rate of all-cause death, cardiac and non-cardiac death | 12 months | 
| Rate of tricuspid valve replacement (TVR) | Rate of clinically-indicated TVR | 12 months | 
| Rate of Revascularisation | Rate of clinically-indicated target lesion revascularisation (TLR) | 12 months | 
| rate of Target vessel failure | Composite of clinically driven TVR, cardiac death or target vessel related MI | 12 months | 
| Rate of Target lesion failure | Composite of clinically driven TLR, cardiac death or target vessel related MI | 12 months | 
| Rate of bleeding | Defined by BARC definition; GUSTO definition and TIMI definition | 12 months | 
| Device success rate | Attainment of < 30% residual stenosis of the target lesion using the assigned study stent only | 12 months | 
| Procedure success rate | Attainment of < 30% residual stenosis of the target lesion using the assigned study stent without occurance of in-hospital MACE | 12 months |