LEADERS FREE II: BioFreedom™ Pivotal Study

A Prospective Study of the BioFreedom™ Biolimus A9™ Drug Coated Stent in Patients at High Risk for Bleeding

This study aims to confirm non-inferiority of the BioFreedom™ Drug Coated Stent to the Gazelle™ Bare Metal Stent arm of the Leaders Free study (NCT01623180) in high bleeding risk patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Coronary Syndrome; High Bleeding Risk
• Intervention / Treatment: Device: BioFreedom™ Drug Coated Coronary Stent System; Drug: Antiplatelet Drug

Detailed Description

In this study all patients will receive the BioFreedom™ Drug Coated Stent and one month of Dual Anti Platelet Therapy

• Study Type: Interventional
• Enrollment (Actual): 1203
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Mazankowski Alberta Heart Institute
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W4
      • Fraser Clinical Trials Inc.
    • Vancouver, British Columbia, Canada, V6E 1M7
      • St. Paul's Hospital
    • Victoria, British Columbia, Canada, V8R 4R2
      • Victoria Heart Institute Foundation
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences
    • Ottawa, Ontario, Canada, K1Y 4W7
      • The University of Ottawa Heart Institute
  • Quebec
    • Montréal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Université de Montréal
    • Montréal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve-Rosemont
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Québec, Quebec, Canada, G1V 4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet Copenhagen University Hospital
• France
  • Aix-en-Provence, France, 13097
    • Clinique Axium
  • Clermont-Ferrand, France, 63050
    • Service de Cardiologie Interventionnelle - Pôle Santé République
  • Fontaine-lès-Dijon, France, 21121
    • Clinique de Fontaine
  • Grenoble, France, 38000
    • Groupe Hospitalier Mutualiste de Grenoble
  • Massy, France, 91300
    • Hôpital Privé Jacques Cartier ICPS
  • Quincy-sous-Sénart, France, 91480
    • Hôpital privé Claude Galien
  • Rouen, France, 76000
    • Clinique Saint Hilaire
  • Toulouse, France
    • CHU Toulouse Rangeuil
• Germany
  • Bad Segeberg, Germany
    • Segeberger Kliniken GmbH
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig GmbH
• Italy
  • Milan, Italy, 20162
    • Grande Ospedale Metropolitano Niguarda
  • Rome, Italy, 00152
    • Azienda Ospedaliera San Camillo Forlanini
• United Kingdom
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital, Dorset Heart Centre
  • Craigavon, United Kingdom, BT63 5QQ
    • Craigavon Cardiac Centre
  • Glasgow, United Kingdom, G81 4DY
    • Golden Jubilee National Hospital
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Tri-Lakes Research
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • La Jolla, California, United States, 92037
      • Scripps Health
    • Santa Barbara, California, United States, 93102
      • Santa Barbara Cottage Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville
    • Sarasota, Florida, United States, 34239
      • Velella Research
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute, Inc.
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • North Georgia Heart Foundation
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Idaho Cardiology Associates
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Jesse Brown VA Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Heart Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Jewish and St. Mary's Hospital
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Bay City, Michigan, United States, 48708
      • McLaren Bay Region
    • Midland, Michigan, United States, 48670
      • MidMichigan Medical Center Midland
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cardiovascular Specialists, LLP
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
  • New York
    • Buffalo, New York, United States, 14203
      • University of Buffalo
    • New York, New York, United States, 10032
      • Columbia University Medical Center/New York Presbyterian Hospital
    • New York, New York, United States, 10021
      • Weill Cornell Medical College-New York Presbyterian
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Heart and Vascular Institute
    • Greensboro, North Carolina, United States, 27401
      • LeBauer Cardiovascular Research Foundation
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research
  • Ohio
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State - Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
    • Reading, Pennsylvania, United States, 19610
      • Berks Cardiologists, Ltd.
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health Cardiovascular Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Cardiovascular Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Heart Institute
    • Knoxville, Tennessee, United States, 37934
      • Tennova Healthcare-Turkey Creek Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Waco, Texas, United States, 76712
      • Providence Health Center
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Any indication for percutaneous coronary intervention with stent placement (PCI-S) in patients deemed at high risk for bleeding and candidates for 1 month dual anti-platelet therapy (DAPT). This includes candidates with stable angina, silent ischemia, acute coronary syndrome (STEMI and non-STEMI), non-native lesions and in-stent restenosis. Patients must provide written informed consent.

Reasons of unsuitability for > 1 month dual antiplatelet treatment must include one or more of the following:

1. Adjunctive oral anticoagulation treatment planned to continue after PCI
2. Age ≥ 75 years old
3. Baseline Hgb <11 g/dl (or anemia requiring transfusion during the 4 weeks prior to the index procedure)
4. Any prior intracerebral bleed
5. Any stroke in the last 12 months
6. Hospital admission for bleeding during the prior 12 months
7. Non skin cancer diagnosed or treated < 3 years, with a perceived increased risk for bleeding
8. Planned daily Nonsteroidal anti-inflammatory drugs (NSAID) (other than aspirin) or steroids for >30 days after PCI
9. Planned surgery that would require interruption of DAPT (within next 6 months)
10. Renal failure defined as: Creatinine clearance <40 ml/min
11. Thrombocytopenia (PLT <100,000/mm3)
12. Severe chronic liver disease defined as: patients who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy or jaundice
13. Expected non-compliance to prolonged DAPT for other medical reasons

Exclusion Criteria:

1. Pregnant and breastfeeding women
2. Patients expected not to comply with 1 month DAPT
3. Patients requiring a planned staged PCI procedure more than one week after the index procedure
4. Procedure planned to require non-study stents, or stand-alone plain old balloon angioplasty (POBA) or stand-alone atherectomy
5. Active bleeding at the time of inclusion
6. Reference vessel diameter <2.25 - >4.0mm
7. Cardiogenic shock
8. Compliance with long-term single anti-platelet therapy unlikely
9. A known hypersensitivity or contraindication to aspirin, clopidogrel (or prasugrel, or ticagrelor if applicable), stainless steel, zinc, Biolimus A9™ or a sensitivity to contrast media, which cannot be adequately pre-medicated
10. PCI during the previous 12 months for a lesion other than the target lesion of the index procedure
11. Participation in another clinical trial (12 months after index procedure)
12. Patients with a life expectancy of < 12 months
13. Patients under judicial protection, tutorship or curatorship (for France only)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BioFreedom™ Drug Coated Stent

Device: BioFreedom™ Drug Coated Coronary Stent System; a non-surgical procedure that uses a catheter to place a stent to open up coronary arteries that have been narrowed by atherosclerosis; Other Names: Coronary Angioplasty; Drug: Antiplatelet Drug; Dual antiplatelet therapy for one month followed by single antiplatelet therapy indefinitely. Aspirin and clopidogrel (or other P2Y12 inhibitor) will be used and dosing is according to standard institutional practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The composite of cardiac death and myocardial infarction at twelve months	12 months
The incidence of clinically driven target lesion revascularization at twelve months	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The composite of cardiac death and myocardial infarction	1, 2, and 6 months and 2 and 3 years
The incidence of clinically driven target lesion revascularization	1, 2, and 6 months and 2 and 3 years
The composite of cardiac death, myocardial infarction and stent thrombosis	1, 2, and 6 months and 1, 2, and 3 years
Bleeding per Bleeding Academic Research Consortium (BARC) Criteria	1, 2, and 6 months and 1, 2, and 3 years
Cardiac Death	1, 2, and 6 months and 1, 2, and 3 years
Myocardial Infarction	1, 2, and 6 months and 1, 2, and 3 years
Stent Thrombosis per Academic Research Consortium (ARC) Definition	1, 2, and 6 months and 1, 2, and 3 years
Urgent target lesion revascularization	1, 2, and 6 months and 1, 2, and 3 years
Clinically driven target lesion revascularization at time points other than primary endpoint	followed for all target lesion revascularizations, up to 3 years
Clinically driven target vessel revascularization	1, 2, and 6 months and 1, 2, and 3 years
All cause mortality	1, 2, and 6 months and 1, 2, and 3 years
Primary endpoints, in patients with at least 1 lesion treated with a trial stent of 3mm or less in nominal diameter	1, 2, and 6 months and 1, 2, and 3 years

Collaborators and Investigators

• Sponsor: Biosensors Europe SA
• Investigators: Study Chair: Martin Leon, Cardiovascular Research Foundation, New York; Principal Investigator: Mitchell Krucoff, Duke University; Principal Investigator: Philip Urban, Hôpital de La Tour

Publications and helpful links

General Publications

• Mehran R, Chandrasekhar J, Urban P, Lang IM, Windhoevel U, Spaulding C, Copt S, Stoll HP, Morice MC; LEADERS FREE Investigators. Sex-Based Outcomes in Patients With a High Bleeding Risk After Percutaneous Coronary Intervention and 1-Month Dual Antiplatelet Therapy: A Secondary Analysis of the LEADERS FREE Randomized Clinical Trial. JAMA Cardiol. 2020 Aug 1;5(8):939-947. doi: 10.1001/jamacardio.2020.0285.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): October 11, 2018
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (Estimate): July 26, 2016

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 1, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Percutaneous Coronary Intervention; Drug Eluting Stent; Acute Coronary Syndrome; Drug Coated Stent
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Hemorrhage; Acute Coronary Syndrome; Platelet Aggregation Inhibitors
• Other Study ID Numbers: 16US01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The emphasis in all scientific publications and presentations will be placed on the 1-year endpoint

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes