Firehawk Rapamycin Target Eluting Coronary Stent North American Trial (TARGET-IV_NA)

Multicenter Randomized Assessment of the Firehawk™ Rapamycin TARGET Eluting Cobalt Chromium Coronary Stent System - North American Trial

The aim of the TARGET-IV NA trial is to demonstrate the clinical non-inferiority of the Firehawk® rapamycin eluting stent system in comparison to currently approved 2nd generation DES for the treatment of subjects with ischemic heart disease (NSTEMI, recent STEMI (>24 hours from initial presentation and in whom enzyme levels have peaked), unstable angina, and stable coronary disease), with atherosclerotic target lesion(s) in coronary arteries with visually estimated reference vessel diameters ≥2.25 mm and ≤4.0 mm.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Microport Firehawk stent; Device: 2nd generation DES (XIENCE family, Promus family, Resolute/Onyx family/Endeavor, and Orsiro stent)

Detailed Description

TARGET-IV NA trial is a prospective, multicenter, 1:1 randomized (Firehawk® vs. 2nd generation DES), trial.

Sub studies:

Angiographic sub study: The first approximately 200 consecutive consenting patients will be enrolled in the angiographic substudy. Optical coherence tomography (OCT) substudy: The first approximately 50 consecutive consenting subjects will be enrolled in the OCT substudy.

Clinical follow-up will be performed at 30 days, 6 months, and 1, 2, 3, 4, and 5 years post randomization. First approximately 200 consecutive consenting patients will undergo planned angiographic follow-up at 13 months after enrollment, with first 50 of these patients also consented to undergo planned OCT at baseline and at 13 months following randomization.

• Study Type: Interventional
• Enrollment (Estimated): 1720
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ming Zheng; Phone Number: +86-21-38954600; Email: mzheng@microport.com

Study Locations

• Belgium
  • Aalst, Belgium
    • Onze Lieve Vrouw Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2W1S7
      • University of Calgary- Foothills Medical Center
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H2A6
      • St. Boniface Hospital Inc.
  • Ontario
    • Newmarket, Ontario, Canada, L3Y2P7
      • York PCI Group INC
  • Qebec
    • Québec, Qebec, Canada, G1V4G5
      • IUPQ
  • Quebec
    • Montréal, Quebec, Canada, H1T1C8
      • Montreal Heart Institute
    • Montréal, Quebec, Canada, H2X0A9
      • CHUM
    • Sherbrooke, Quebec, Canada, J1J3H5
      • CIUSSE de l'estrie CHUS
• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Copenhagen University Hospital - Rigshospitalet
  • Odense, Denmark
    • Odense University Hospital
  • Roskilde, Denmark
    • Roskilde University Hospital
• Netherlands
  • Nijmegen, Netherlands
    • Radbout UMC
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology PC
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Mercy Gilbert Medical Center
  • California
    • La Jolla, California, United States, 90903
      • UC San Diego School of Medicine
    • Riverside, California, United States, 92501
      • Riverside Community Hospital
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale New Heaven Hospital
  • Florida
    • Atlantis, Florida, United States, 33462
      • JFK Medical Center
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular Consultants
    • Clearwater, Florida, United States, 33756
      • CCC Research - Countryside
    • Jacksonville, Florida, United States, 32216
      • Memorial Hospital Jacksonville
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Veterans Affairs Medical Center
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Elkhart General Hospital
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Heart Center of Indiana
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center-Northern Light Cardiology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center, Inc.
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 13203
      • St. Joseph Mercy Hospital
    • Bay City, Michigan, United States, 48708
      • McLaren Bay
    • Lansing, Michigan, United States, 48910
      • Mclaren Greater Lansing
    • Petoskey, Michigan, United States, 49770
      • McLaren Northern Michigan
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Metropolitan Heart Vascular Institute
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • St Dominic Hospital
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Boone Hospital Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan Medical Center East
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center/NYPH
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital & Heart Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Mercy Health St. Vincent Medical Center LLC
  • Pennsylvania
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Erie, Pennsylvania, United States, 16550
      • UPMC Hamot
    • Harrisburg, Pennsylvania, United States, 17104
      • UPMC Harrisburg Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • Tennessee
    • Knoxville, Tennessee, United States, 37934
      • Turkey Creek Medical Center
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor Heart and Vascular Hospital
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health
    • Tyler, Texas, United States, 75701
      • East Texas Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Charleston Area Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Patient understands the trial requirements and treatment procedures and provides written informed consent prior to any trial-specific tests or treatment.
3. Patients with an indication for PCI including angina (stable or unstable), silent ischemia (in absence of symptoms a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or a positive coronary physiology test (e.g. FFR≤0.80 or iFR<0.90 or rFR ≤ 0.89 must be present), NSTEMI, or recent STEMI (STEMI >24 hours and in whom enzyme levels have peaked). For STEMI the time of presentation to the first treating hospital, whether a transfer facility or the study hospital, must be >24 hours prior to randomization and enzyme levels (CK-MB or Troponin) demonstrating that either or both enzyme levels have peaked.
4. Patient is willing to comply with all protocol-required follow-up evaluations.

Angiographic inclusion criteria:

1. Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.25 mm to ≤4.0 mm and up to 44 mm in length.
2. The coronary anatomy is deemed likely to allow delivery of a study device to the target lesion(s).
3. Complex lesions are allowed including calcified lesions (lesion preparation is allowed and strongly recommended with current approved devices (e.g. scoring/cutting balloon and rotational/orbital atherectomy), multivessel disease, CTO,bifurcation lesions (except planned dual stent implantation), ostial lesions, tortuous lesions, and protected left main lesions.
4. Overlapping stents are allowed

Exclusion Criteria:

1. STEMI within 24 hours of initial time of presentation to the first treating hospital, whether at a transfer facility or the study hospital or in whom enzyme levels (either CK-MB or Troponin) have not peaked.
2. PCI within the 24 hours preceding the baseline procedure.
3. History of stent thrombosis.
4. Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP.
5. Subject is intubated.
6. Known LVEF <30%.
7. Subject has a known allergy to contrast (that cannot be adequately pre-medicated) and/or the trial stent system or any protocol-required concomitant medications or devices (e.g. cobalt chromium alloy, stainless steel, sirolimus, everolimus or structurally related compounds, polymer, any P2Y12 inhibitor, or aspirin).
8. Planned surgery within 6 months.
9. Subject has an indication for chronic oral anticoagulant treatment (with either vitamin K antagonists or novel anticoagulants - NOACs)
10. Calculated creatinine clearance <30 mL/min using Cockcroft-Gault equation (<40 mL/min for subjects participating in the angiographic follow-up sub-study).
11. Hemoglobin <10 g/dL.
12. Platelet count <100,000 cells/mm3 or >700,000 cells/mm3.
13. White blood cell (WBC) count <3,000 cells/mm3.
14. Clinically significant liver disease.
15. Active peptic ulcer or active bleeding from any site.
16. Other serious medical illness with a life-expectancy < 24 months (e.g. cancer, severe heart failure, severe lung disease).
17. A planned procedure that may cause non-compliance with the protocol or confound data interpretation.
18. Participation in another investigational drug or device trial that has not yet reached its primary endpoint and that may interfere with protocol compliance or confound data interpretation (as per the opinion of the investigator); or intent to participate in another investigational drug or device trial within 12 months.
19. Intention to become pregnant within 12 months (women of child-bearing potential who are sexually active must agree to use contraceptives from the time of enrollment through 12 months post-procedure).
20. Pregnancy or nursing (women of child-bearing potential must have a pregnancy test within 7 days prior to the index procedure).
21. Any co-morbid condition that may cause non-compliance with the protocol (e.g. dementia, substance abuse, etc.).
22. Subject has received an organ transplant or is on a waiting list for an organ transplant.
23. Subject is receiving oral or intravenous immunosuppressive therapy or has known life-limiting immunosuppressive or autoimmune disease (e.g., HIV). Corticosteroids are allowed.

Angiographic Exclusion Criteria:

1. Unprotected left main interventions
2. Bifurcation lesions with intended dual stent implantations
3. DES restenotic lesions
4. Prior PCI in the target vessel in the 12 months prior to enrollment
5. Any lesion in the target vessel that is likely to require PCI within 12 months
6. Stent lengths >36mm for diameters 2.0 mm and 2.25 mm (i.e., very long thin stents).
7. Lesion with intended ≥ 3 stent implantation

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: Firehawk group; Participants implant Firehawk stent(s)	Device: Microport Firehawk stent; MicroPort Firehawk biodegradable polymer rapamycin target eluting stent; Other Names: MicroPort Firehawk rapamycin target eluting stent
Active Comparator: 2nd generation DES; Participants implant Everolimus eluting stents (Xience family - Abbott Vascular, Promus family- Boston Scientific, Synergy - Boston Scientific), or Zotarolimus eluting stents (Resolute/Onyx family and Endeavor- Medtronic), or Sirolimus eluting stents (Orsiro- Biotronik)	Device: 2nd generation DES (XIENCE family, Promus family, Resolute/Onyx family/Endeavor, and Orsiro stent); Everolimus eluting stents (Xience family - Abbott Vascular, Promus family- Boston Scientific, Synergy - Boston Scientific); Zotarolimus eluting stents (Resolute/Onyx family and Endeavor- Medtronic); Sirolimus eluting stents (Orsiro- Biotronik)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Lesion Failure	Percentage of participants that had either Cardiac Death, Myocardial Infarction (not clearly attributable to a non-target vessel)or Target Lesion Revascularization (TLR, clinically indicated) after one year	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-stent late loss	In-stent late loss at 13 months post-procedure as measured by quantitative coronary angiography (QCA)	13 months
Neointimal thickness	Neointimal thickness at 3 months measured by Optical Coherence Tomography (OCT)	13 months
Target Lesion Failure	Percentage of participants that had either Cardiac Death, Myocardial Infarction (not clearly attributable to a non-target vessel)or Target Lesion Revascularization (TLR, clinically indicated)	12 months and yearly thereafter until 5 years
Target vessel failure	Percentage of participants that had either cardiac death, target vessel-related MI*, or ischemia-driven target-vessel revascularization	12 months and yearly thereafter until 5 years
Major adverse cardiac events (MACE)	Percentage of participants that had either cardiac death, target vessel-related MI*, or ischemia-driven target-vessel revascularization	12 months and yearly thereafter until 5 years
All-cause mortality	mortality rate	12 months and yearly thereafter until 5 years
Cardiac death	Cardiac death rate	12 months and yearly thereafter until 5 years
Q-wave MI	percentage of participants that had Q-wave MI	12 months and yearly thereafter until 5 years
Non Q-wave MI	percentage of participants that had Non Q-wave MI	12 months and yearly thereafter until 5 years
Any MI	percentage of participants that had any MI	12 months and yearly thereafter until 5 years
Target vessel MI	percentage of participants that had MI related to target vessel	12 months and yearly thereafter until 5 years
Any revascularization	percentage of participants that had any revascularization	12 months and yearly thereafter until 5 years
Ischemia-driven TLR	percentage of participants that had Ischemia-driven TLR	12 months and yearly thereafter until 5 years
Probable stent thrombosis	percentage of participants that had Probable stent thrombosis	12 months and yearly thereafter until 5 years
Definite stent thrombosis	percentage of participants that had Definite stent thrombosis	12 months and yearly thereafter until 5 years

Collaborators and Investigators

• Sponsor: Shanghai MicroPort Medical (Group) Co., Ltd.
• Investigators: Study Chair: Martin Leon, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: TARGET-IV_NA

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