Bioflow-DAPT Study

• ClinicalTrials.gov Identifier: NCT04137510
• Recruitment Status: Active, not recruiting
• First Posted: October 24, 2019
• Last Update Posted: April 12, 2023
• Sponsor: Biotronik AG
• Information provided by (Responsible Party): Biotronik AG

Tracking Information

• First Submitted Date: October 22, 2019
• First Posted Date: October 24, 2019
• Last Update Posted Date: April 12, 2023
• Actual Study Start Date: February 24, 2020
• Actual Primary Completion Date: January 1, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 14, 2023): Composite of cardiac death, myocardial infarction (MI) and definite or probable stent thrombosis at 12 months [ Time Frame: 12 months post-procedure ]
• Original Primary Outcome Measures (submitted: October 22, 2019): cardiac death, myocardial infarction (MI) and definite or probable stent thrombosis at 12 months [ Time Frame: 12 months post-procedure ]

Current Secondary Outcome Measures (submitted: October 23, 2019)

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

Original Secondary Outcome Measures (submitted: October 22, 2019)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bioflow-DAPT Study
• Official Title: 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)

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Prospective, multi-center, international, two-arm randomized controlled clinical study.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Coronary Artery Disease

Intervention

Device: Percutaneous coronary intervention

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.

Study Arms

• Experimental: Orsiro
  Intervention: Device: Percutaneous coronary intervention
• Active Comparator: Resolute Onyx
  Intervention: Device: Percutaneous coronary intervention

• Publications *: Capodanno D. Another Coronary Stent for Patients at High Bleeding Risk. JACC Cardiovasc Interv. 2021 Sep 13;14(17):1884-1887. doi: 10.1016/j.jcin.2021.07.028. No abstract available.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 22, 2019): 1948
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 19, 2027
• Actual Primary Completion Date: January 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subject is acceptable candidate for treatment with a DES

2. Subject is considered at high bleeding risk (HBR), defined as meeting one or more of the following criteria at the time of enrollment:

   1. ≥ 75 years of age
   2. Moderate (estimated GFR 30-59 ml/min) or severe (estimated GFR < 30 ml/min) chronic kidney disease or failure (dialysis dependent)
   3. Advanced liver disease, defined as having cirrhosis with or without portal hypertension and with or without gastroesophageal varices.
   4. Cancer (excluding non-melanoma skin cancer) diagnosed or treated within the previous 12 months or actively treated
   5. Anemia with hemoglobin < 11.0 g/dL or requiring transfusion within 4 weeks prior to randomization
   6. Baseline thrombocytopenia defined as a platelet count <100,000/mm3
   7. 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
   8. History of hospitalization for bleeding within the previous 12 months
   9. Chronic clinically significant bleeding diathesis
   10. Clinical indication for chronic or lifelong oral anticoagulation (OAC) (with a vitamin K antagonist or non-vitamin K OAC)
   11. Clinical indication for chronic or lifelong steroid or oral nonsteroidal anti-inflammatory drug(s) (NSAIDs), other than aspirin
   12. Nondeferrable major surgery on DAPT
   13. Recent major surgery or major trauma within 30 days before PCI
   14. Precise DAPT score ≥ 25
3. Subject is ≥ 18 years or the minimum age required for legal adult consent in the country of enrollment
4. 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
5. Subject is willing to comply with all protocol and follow-up requirements, including agreement to discontinue DAPT at 1 month
6. Subject is eligible for dual antiplatelet therapy treatment with aspirin plus a P2Y12 inhibitor agent for 1-month post index procedure

Exclusion Criteria:

1. Subject who previously experienced a stent or scaffold thrombosis in any coronary vessel
2. 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
3. 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. 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
5. Subject judged by physician as inappropriate for discontinuation from DAPT at 1 month following index procedure, due to another condition requiring chronic DAPT
6. 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
7. Active bleeding at the time of inclusion
8. Subject with a current medical condition with a life expectancy of less than 12 months
9. 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
10. Subject is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study
11. In the investigator's opinion, subject will not be able to comply with the follow-up requirements
12. Subjects who need an impartial witness to give an informed consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Denmark, France, Germany, Hong Kong, Hungary, Italy, Latvia, Malaysia, Netherlands, New Zealand, Poland, Singapore, Spain, Switzerland, Thailand

Administrative Information

• NCT Number: NCT04137510
• Other Study ID Numbers: C1703
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Biotronik AG
• Original Responsible Party: Same as current
• Current Study Sponsor: Biotronik AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Marco Valgimigli, Prof. Dr.; Cardiocentro Ticino, Via Tesserete 48, 6900 Lugano, Switzerland

• PRS Account: Biotronik AG
• Verification Date: April 2023