Bioflow-DAPT Study

Study Overview
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Brief Summary
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BIOFLOW-DAPT is a prospective, multi-center, international, two-arm randomized controlled clinical study. A total of 1'948 subjects will be randomized 1:1 to receive either Orsiro Mission 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. Clinical follow-up visits will be scheduled at 1, 6 and 12 months post-procedure.

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

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Percutaneous coronary intervention


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 30-59 ml/min) or severe (estimated GFR < 30 ml/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 hemoglobin < 11.0 g/dL or requiring transfusion within 4 weeks prior to randomization Baseline thrombocytopenia defined as a platelet count <100,000/mm3 History of stroke (ischemic or hemorrhagic), previous intracerebral hemorrhage (ICH) (spontaneous at any time or traumatic within the past 12 months) or presence of a brain arteriovenous malformation History of hospitalization for bleeding within the previous 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) Clinical indication for chronic or lifelong steroid or oral nonsteroidal anti-inflammatory drug(s) (NSAIDs), other than aspirin Nondeferrable major surgery on DAPT Recent major surgery or major 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 authorized 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 aspirin 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 irridium, silicon carbide, PLLA,polymers, mTOR inhibiting drugs such as zotarolimus or sirolimus, or contrast media Revascularization of any target vessel within 9 months prior to the index procedure or previous PCI of any non-target vessel within 72 hours prior to or during the index procedure 4. Subject with documented left ventricular ejection 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 the 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's opinion, subject will not be able to comply with the follow-up requirements Subjects who need an impartial witness to give an informed consent

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, international, two-arm randomized controlled clinical study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orsiro<br> | Device: Percutaneous coronary intervention<br>* It's a non-surgical procedure that uses a catheter to place a stent into a coronary blood vessel in order to open up the vessel.<br>|
| Active Comparator: Resolute Onyx<br> | Device: Percutaneous coronary intervention<br>* It's a non-surgical procedure that uses a catheter to place a stent into a coronary blood vessel in order to open up the vessel.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of cardiac death, myocardial infarction (MI) and definite or probable stent thrombosis at 12 months |  | 12 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of definite/probable stent thrombosis according to the ARC definition |  | until 12 months post-procedure | 
| Rate of MACCE | composite of all-cause death, MI, and stroke | until 12 months post-procedure | 
| Rate of MACE | composite of cardiac death, MI, and Target Vessel Revascularization (TVR) | until 12 months post-procedure | 
| Rate of cardiac death or MI | all, target vessel related MI, Q-wave and non Q-wave, ST-related and non ST-related | until 12 months post-procedure | 
| Rate of all-cause death, cardiac, non-cardiac |  | until 12 months post-procedure | 
| Rate of stroke, ischemic and hemorrhagic |  | until 12 months post-procedure | 
| Rate of clinically-indicated TVR |  | until 12 months post-procedure | 
| Rate of clinically-indicated Target Lesion Revascularization (TLR) |  | until 12 months post-procedure | 
| Rate of Target Vessel Failure (TVF) | Composite of clinically-driven TVR, cardiac death or target-vessel related MI | until 12 months post-procedure | 
| Rate of target lesion failure (TLF) | Composite of clinically driven TLR, cardiac death or target vessel related MI | until 12 months post-procedure | 
| Rate of bleeding according to BARC definition |  | until 12 months post-procedure | 
| Rate of bleeding according to GUSTO definition |  | until 12 months post-procedure | 
| Rate of bleeding according to TIMI definition |  | until 12 months post-procedure | 
| Rate of Device success | Attainment of less than 30% residual stenosis of the target lesion using assigned stent only | until 12 months post-procedure | 
| Rate of Procedure success | Attainment of less than 30% residual stenosis of the target lesion using assigned stent only without occurrence of in-hospital major adverse cardiac events | until 12 months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBR, DAPT, Dual antiplatelet therapy, high bleeding risk, Coronary artery disease, Percutaneous coronary intervention, PCI