Bioflow-DAPT Study

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Percutaneous coronary intervention

• Study Type: Interventional
• Enrollment (Actual): 1948
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Epping, Australia, 3076
    • The Northern Hospital
  • New Lambton, Australia, 2305
    • John Hunter Hospital
  • Perth, Australia, 6000
    • Royal Perth Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz
  • Salzburg, Austria, 5020
    • Uniklinikum Salzburg
• Belgium
  • Brugge, Belgium, 8000
    • AZ St Jan Brugge
  • Genk, Belgium, 3600
    • Ziekenhuis Oost Limburg Genk
  • Roeselare, Belgium, 8800
    • AZ Delta
  • Woluwe-Saint-Lambert, Belgium, 1200
    • UCL St Luc
• Denmark
  • Hellerup, Denmark, 2900
    • Herlev og Gentofte Hospital
  • Roskilde, Denmark, 4000
    • Roskilde University Hospital
• France
  • Brest, France, 29601
    • CHU Brest
  • Lille, France, 59000
    • Centre Hospitalier Universitaire de Lille
  • Massy, France, 91300
    • Hôpital privé Jacques Cartier
  • Nîmes, France, 30029
    • CHU Nîmes
  • Paris, France, 75004
    • Assistance Publique Hopitaux De Paris
  • Paris, France, 75004
    • Assistance Publique Hopitaux de Paris (APHP)
  • Rouen, France, 76000
    • Clinique Saint Hilaire
  • Toulouse, France, 31076
    • Clinique Pasteur
  • Toulouse, France, 31400
    • CHU de Toulouse
  • Tours, France, 37044
    • CHRU De Tours
• Germany
  • Bad Segeberg, Germany, 23795
    • Segeberger Kliniken
  • Berlin, Germany, 13353
    • Charite Virchow-Klinikum
  • Essen, Germany, 45138
    • Contilla Herz- und Gefäßzentrum, Elisabeth-Krankenhaus
  • Friedrichshafen, Germany, 88048
    • Klinikum Friedrichshafen GmbH
  • Neuss, Germany, 41464
    • Städtische Kliniken Neuss, Lukaskrankenhaus GmbH
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, Hong Kong
    • The Chinese University of Hong Kong
• Hungary
  • Budapest, Hungary, 1124
    • Semmelweis University
  • Kaposvár, Hungary, 7400
    • Somogy County Kaposi Mór Teaching Hospital
  • Pécs, Hungary, 7624
    • University of Pecs
• Italy
  • Catania, Italy, 95125
    • Azienda Ospedaliero - Universitaria Policlinico - Vittorio
  • Milano, Italy, 20138
    • Centro Cardiologico Monzino
  • Pavia, Italy, 27100
    • IRCCS Fondazione Policlinico "San Matteo"
  • Torrette, Italy, 60126
    • Azienda Ospedaliero-Universitaria
• Latvia
  • Engure, Latvia, LV-3113
    • Sia AK Medical Solutions
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara
• Netherlands
  • Den Haag, Netherlands, 2545 AA
    • Haga ziekenhuis
• New Zealand
  • Auckland, New Zealand, 1142
    • Auckland City Hospital
• Poland
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla
  • Lubin, Poland, 59-301
    • Miedziowe Centrum Zdrowia
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
• Spain
  • Santander, Spain, 39008
    • Hospital Universitario Marques De Valdecilla
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de la Valencia
  • Vitoria, Spain, 01009
    • Hospital Universitario Araba
• Switzerland
  • Genève, Switzerland, 1211
    • Hopitaux universitaires de Geneve
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaires Vaudoise
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
  • Morges, Switzerland, 1110
    • Hôpital de Morges
  • Zürich, Switzerland, 8063
    • Stadtspital Triemli
• Thailand
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital
  • Bangkok, Thailand, 11000
    • Central Chest Institute of Thailand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orsiro	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.
Active Comparator: Resolute Onyx	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Biotronik AG

Publications and helpful links

General Publications

• Tchekmedyian V. Salivary Gland Cancers. Hematol Oncol Clin North Am. 2021 Oct;35(5):973-990. doi: 10.1016/j.hoc.2021.05.011.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): January 1, 2023
• Study Completion (Anticipated): February 19, 2027

Study Registration Dates

• First Submitted: October 22, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: PCI; Coronary artery disease; Percutaneous coronary intervention; Dual antiplatelet therapy; DAPT; high bleeding risk; HBR
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: C1703

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