PIONEER III Trial to Assess Safety and Efficacy of the BuMA Supreme™ Drug Coated Coronary Stent in Patients With Coronary Disease

A Prospective Global Randomized Trial Assessing the Safety and Efficacy of the BuMA Supreme™ Biodegradable Drug Coated Coronary Stent System for Coronary Revascularization in Patients With Stable Coronary Artery Disease or Non-ST Segment Elevation Acute Coronary Syndromes

The primary objective of this trial is to compare the safety and efficacy of the SINOMED BuMA Supreme biodegradable coronary stent in patients with up to 3 coronary lesions to either the XIENCE or Promus durable polymer coronary stents.

This prospective, global, multi-center, randomized 2:1, single blind study will enroll up to 1632 subjects at up to 130 investigational sites in North America, Japan, and Europe. Subjects will have clinical follow-up in-hospital and at 30 days, 6 months, 12 months, and 2, 3, 4, and 5 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: BuMA Supreme DES; Device: Xience or Promus DES

• Study Type: Interventional
• Enrollment (Actual): 1632
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Imelda
  • Charleroi, Belgium
    • Chu Charleroi
  • Genk, Belgium, 3600
    • Ziekenhuis Oost Limburg Genk
  • Hasselt, Belgium, 3500
    • Jessa hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N-2T9
      • Foothills Medical Centre
  • Ontario
    • Toronto, Ontario, Canada, M5B-1W8
      • St. Michael's Hospital
• Japan
  • Kamakura City
    • Kanagawa, Kamakura City, Japan, 247-8533
      • Shonan Kamakura General Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
  • Leeuwarden, Netherlands
    • MCL
  • Rotterdam, Netherlands
    • Maasstad Ziekenhuis
• Spain
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Instituto de Investigación Hospital 12 de Octubre
  • Vigo, Spain, 36312
    • Hospital Álvaro Cunqueiro
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern
  • Geneva, Switzerland, 1211
    • University Hospital Geneva HUG, Clinic for Cardiology
• United Kingdom
  • London, United Kingdom
    • St Bartholomew'S Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology, PC
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Dignity Health - Mercy Gilbert Medical Center / Chandler Regional Medical Center
  • California
    • Los Angeles, California, United States, 90048
      • Smidt Heart Institute Cedars-Sinai Maedical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington HWospital Center
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Bethesda Hospital East/Daniel Heart and Vascular Center
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular Consultants
    • Ocala, Florida, United States, 34471
      • Mediquest Research Group Inc.
    • Panama City, Florida, United States, 32401
      • Cardiovascular Institute of Northwest Florida
    • Tampa, Florida, United States, 33613
      • Florida Hospital Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Krannert Institute of Cardiology
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent's Medical Group
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iowa Heart Center
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Brownsboro Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • MedStar Union Memorial Hospital
  • Michigan
    • Petoskey, Michigan, United States, 49770
      • Northern Michigan Hospital d.b.a. McLaren Northern Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
    • Ypsilanti, Michigan, United States, 48197
      • Michigan Heart
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essential Health
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North MS Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • CHI Health Research Center
  • New Jersey
    • Haddon Heights, New Jersey, United States, 08035
      • Cardiovascular Associates of Delaware Valley
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center / New York Presbyterian Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
    • Cincinnati, Ohio, United States, 45219
      • Lindner Research Center
    • Elyria, Ohio, United States, 44035
      • North Ohio Heart
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Toledo, Ohio, United States, 43608
      • Mercy St. Vincent Medical Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Clinic
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Wyomissing, Pennsylvania, United States, 19610
      • Berks Cardiologists, Ltd.
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • Texas
    • Tyler, Texas, United States, 75701
      • Tyler Cardiovascular Consultants
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Winchester, Virginia, United States, 22601
      • Winchester Medical Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patient is a male or non-pregnant female ≥20 years of age.
2. The patient has symptomatic ischemic heart disease, including chronic stable angina (and/or objective evidence of myocardial ischemia on functional study or invasive fractional flow reserve [FFR] measurement) or acute coronary syndromes (UA or NSTEMI), that requires elective or urgent percutaneous coronary intervention (PCI).
3. The patient is an acceptable candidate for percutaneous coronary intervention (PCI) with drug-eluting stents, and for emergent coronary bypass graft (CABG) surgery.
4. The patient is willing to comply with specified follow-up evaluations.
5. The patient or legally authorized representative has been informed of the nature of the study, agrees to its provisions, and has been provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).

Exclusion Criteria:

1. Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following index procedure. Female patients of childbearing potential must have a negative pregnancy test done within 7 days prior to index procedure per site standard test.
2. Patients with a history of bleeding diathesis or coagulopathy, contraindications to anti-platelet and/or anticoagulant therapy, or who will refuse transfusion.
3. Patients who are receiving or will require chronic anticoagulation therapy for any reason.
4. Known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, ADP receptor antagonists (clopidogrel, prasugrel, ticagrelor, ticlopidine), cobalt chromium, 316L stainless steel or platinum, sirolimus or its analogues, and/or contrast sensitivity that cannot be adequately pre-medicated.
5. ST-segment elevation myocardial infarction (STEMI) at index presentation or within 7 days prior to randomization.
6. Known LVEF <30% or cardiogenic shock requiring pressors or mechanical circulatory assistance (e.g., intra-aortic balloon pump, left ventricular assist device, other temporary cardiac support blood pump).
7. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation or Cockcroft-Gault formula) or dialysis at the time of screening.
8. Target vessel percutaneous coronary intervention with stent placement in the previous 3 months.
9. Planned elective surgery that would require discontinuation of DAPT within 6 months of the index procedure.
10. Past or pending heart or any other organ transplant, or on the waiting list for any organ transplant.
11. Patients who are receiving immunosuppressant therapy, or who have known immunosuppressive or severe autoimmune disease that will require chronic immunosuppressive therapy. NOTE: Corticosteroid use is permitted.
12. Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol, confound data interpretation, or is associated with a life expectancy of less than 1 year.
13. Current participation in another investigational drug or device study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BuMA Supreme Coronary Stent System	Device: BuMA Supreme DES; Implant BuMA Supreme stent only
ACTIVE_COMPARATOR: Xience or Promus Everolimus Stent System	Device: Xience or Promus DES; Implant XIENCE family or Promus family only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion failure (TLF)	defined as the composite of cardiac death, target vessel related myocardial infarction (TV-MI), and clinically-driven target lesion revascularization (TLR)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Safety and Efficacy defined as target lesion failure (TLF) between 12 months and 5 years by landmark analysis	TLF is defined as the composite of cardiac death, target vessel related myocardial infarction (TV-MI), and clinically-driven target lesion revascularization (TLR)	Between 12 months and 5 years
Major adverse cardiac events (MACE)	defined as a composite of all-cause death, myocardial infarction, and target vessel revascularization	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Mortality	classified as cardiac or non-cardiac, and reported cumulatively and individually	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Myocardial infarction (MI)	defined according to the modified Third Universal Definition	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Stent thrombosis	definite or probable (ARC-defined), classified as early, late, or very late	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Bleeding complications (BARC definitions)	evaluated as components and as a composite of BARC Type 3 and 5 bleeding	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Lesion success	defined as attainment of <30% residual stenosis, as measured by quantitative coronary angiography (QCA) using any percutaneous method [evaluated post-procedure]	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Device success	defined as attainment of <30% residual stenosis of the target lesion measured by QCA using the assigned device [evaluated post-procedure]	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Procedure success	defined as lesion success without the occurrence of in-hospital MACE [evaluated in-hospital]	30 days, 6 months, 12 months, and 2, 3, 4, and 5 years
Clinically-driven target lesion revascularization (TLR)	[evaluated in hospital and at 30 days, 6 months, and 1, 2, 3, 4 and 5 years]	30 days, 6 months, and 1, 2, 3, 4, and 5 years
Clinically-driven target vessel revascularization (TVR)	[evaluated in hospital and at 30 days, 6 months, and 1, 2, 3, 4 and 5 years]	30 days, 6 months, and 1, 2, 3, 4, and 5 years
Target vessel failure (TVF)	defined as cardiac death, target vessel-related MI, or clinically-driven target vessel revascularization [evaluated in hospital and at 30 days, 6 months, and 1, 2, 3, 4 and 5 years]	30 days, 6 months, and 1, 2, 3, 4, and 5 years
Target Lesion Failure (TLF)	defined as cardiac death, target vessel-related MI, or clinically-driven target lesion revascularization [evaluated in hospital and at 30 days, 6 months, and 2, 3, 4 and 5 years]	30 days, 6 months, and 2, 3, 4, and 5 years

Collaborators and Investigators

• Sponsor: Sino Medical Sciences Technology Inc.
• Collaborators: Nova Vascular LLC
• Investigators: Study Chair: Martin B Leon, MD, Center for Interventional Vascular Therapy - Columbia University Medical Center / New York-Presbyterian Hospital, United States; Principal Investigator: Dean Kereiakes, MD, The Christ Hospital Physicians - Ohio Heart & Vascular, United States; Principal Investigator: Stephan Windecker, MD, Bern University Hospital Department for Cardiology, Switzerland

Publications and helpful links

General Publications

• Lansky AJ, Kereiakes DJ, Baumbach A, Windecker S, Hussain Y, Pietras C, Dressler O, Issever O, Curtis M, Bertolet B, Zidar JP, Smits PC, Alfonso Jimenez Diaz V, McLaurin B, Hofma S, Cequier A, Dib N, Benit E, Mathur A, Brogno D, Berland J, Wykrzykowska J, Piegari G, Brugaletta S, Saito S, Leon MB; PIONEER III Trial Investigators. Novel Supreme Drug-Eluting Stents With Early Synchronized Antiproliferative Drug Delivery to Inhibit Smooth Muscle Cell Proliferation After Drug-Eluting Stents Implantation in Coronary Artery Disease: Results of the PIONEER III Randomized Clinical Trial. Circulation. 2021 Jun;143(22):2143-2154. doi: 10.1161/CIRCULATIONAHA.120.052482. Epub 2021 Apr 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 13, 2017
• Primary Completion (ACTUAL): October 1, 2020
• Study Completion (ANTICIPATED): September 1, 2024

Study Registration Dates

• First Submitted: May 23, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (ACTUAL): May 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 12, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Drug-eluting stent
• 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: SIN-US-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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