HARMONEE - Japan-USA Harmonized Assessment by Randomized, Multi-Center Study of OrbusNEich's Combo StEnt

NCT02073565 | Completed Results DMC

• 2 other identifiers: VP-0601OMKK 02
• Study Type: interventional
• Target: 572
• Locations: 2 countries
• Sites: 50

Brief Summary

This is a multi-center, single-blind, randomized, active-controlled, clinical trial in Percutaneous Coronary Intervention (PCI) subjects. Subjects will be randomized to receive the Combo stent as the investigational treatment arm or an Everolimus Eluting Stent (EES) as the active-control arm.

Conditions

Coronary Arteriosclerosis; Non ST Segment Elevation Acute Coronary Syndrome

Keywords

intracoronary stent; drug eluting stent; sirolimus; endothelial progenitor cells

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Target Vessel Failure (TVF)

  The primary clinical endpoint of Target Vessel Failure (TVF), defined as cardiac death, target-vessel myocardial infarction (MI), or ischemia-driven Target Vessel Revascularization(TVR) by percutaneous or surgical methods, at 1 year.

  1 year follow-up

Secondary Outcomes (1)

• Percentage of Healthy Tissue Coverage That Was Greater Than 40 Micrometers

  1 year

Other Outcomes (2)

• Number of Patients With Clinically and Functionally Ischemia-Driven Target Lesion Revascularization (TLR)

  1 year

• Number of Patients Exhibiting Human Antimurine Antibody (HAMA) Reaction

  Day of device implantation, 30 days, 12 months

Study Arms (2)

Combo

EXPERIMENTAL

The Combo Stent is composed of the OrbusNeich R stent™, with an abluminal coating of a bioabsorbable polymer matrix formulated with sirolimus for sustained release, and an anti-CD34 antibody cell capture coating on the luminal surface.

Device: OrbusNeich Combo stent™

Everolimus Eluting Stent (EES)

ACTIVE COMPARATOR

Everolimus Eluting Stent (EES) (Xience V, Xience Prime, Xience Xpedition stents, Abbott Vascular/Abbott Vascular Japan). Xience Prime inherited the clinical result of Xience V and is a product that obtains efficiency essentially equal to Xience V.

Device: Everolimus Eluting Stent (EES)

Interventions

OrbusNeich Combo stent™ DEVICE

The Combo Stent is composed of the OrbusNeich R stent™, with an abluminal coating of a bioabsorbable polymer matrix formulated with sirolimus for sustained release, and an anti-CD34 antibody cell capture coating on the luminal surface.

Combo

Everolimus Eluting Stent (EES) DEVICE

Everolimus Eluting Stent (EES) (Xience V, Xience Prime, Xience Xpedition stents, Abbott Vascular/Abbott Vascular Japan). Xience Prime inherited the clinical result of Xience V and is a product that obtains efficiency essentially equal to Xience V.

Everolimus Eluting Stent (EES)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for this trial, subjects must meet all of the following criteria:
• Subject is able to verbally confirm understanding of risks, benefits, and treatment alternatives of Combo vs EES stent, and the subject or a legally authorized representative (LAR) must provide written informed consent before any study-related procedures are performed.
• Subject must be at least 20 years of age at the time of randomization.
• Subject must have clinical or functional evidence of myocardial ischemia (eg, stable or unstable angina, stabilized non-ST-elevation myocardial infarction confirmed by serum markers, ischemia by positive functional study, abnormal FFR, or a reversible change in the electrocardiogram (ECG) consistent with ischemia).
• Subject must be acceptable candidate with anatomy suitable for PCI with a DES.
• Subject agrees to return for all study-related follow-up assessments, including invasive OCT follow-up assessment at 6 months (Cohort A) and at 1 year postprocedure (Cohorts A, B, and C).
• Subject is an acceptable candidate for Coronary artery bypass grafting (CABG) surgery.
• Angiographic Anatomy Criteria-
• Target lesions must be located in a native coronary artery with visually estimated diameter of 2.5 mm to 3.5 mm, inclusive, and up to 3 de novo target lesions may be treated, with a maximum of 2 de novo target lesions per epicardial vessel, with a maximum of 2 target vessels.
• Target lesions should be treatable with a single stent, and must measure 28 mm or less in length by visual estimation (2 mm or more of nondiseased tissue on either side of the target lesion should be covered by the study stent).
• If more than 1 target lesion will be treated, the reference vessel diameter and lesion length of each target lesion must meet the above criteria.
• Target lesions must be in a major artery or branch with a visually estimated stenosis of 50% or greater and less than 100% with a Thrombolysis in Myocardial Infarction (TIMI) flow of 1 or greater.
• Previous percutaneous intervention of lesions in a target vessel (including side branches) is allowed if done 9 or more months before the study procedure and greater than 10 mm from the current target lesion.
• Nonstudy percutaneous interventions for lesions in a nontarget vessel are allowed if done 9 or more months before the study procedure, in the absence of documented ischemia or angiographic restenosis related to the vessel.

You may not qualify if:

• If a subject meets any of the following criteria, he or she may not be enrolled in the study:
• ST-Elevation Myocardial Infarction (STEMI) at index presentation or within 7 days of study screening.
• Subject has current unstable arrhythmias or intractable angina with ECG changes or shock requiring pressors or mechanical assist device (intraaortic balloon pump, left ventricular assist device, Impella, etc.).
• Subject has known left ventricular ejection fraction (LVEF) less than 30%.
• Subject has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant.
• Subject is receiving or scheduled to receive anticancer therapy for malignancy within 30 days before or after the procedure.
• Subject is receiving immunosuppression therapy, has known serious immunosuppressive disease (eg, human immunodeficiency virus), or has severe autoimmune disease that requires chronic immunosuppressive therapy (eg, systemic lupus erythematosus).
• Subject has known hypersensitivity or contraindication to aspirin; both heparin and bivalirudin; all available P2Y12 inhibitors (clopidogrel, prasugrel, ticlopidine, and ticagrelor); any everolimus, sirolimus, cobalt, chromium, nickel, tungsten, acrylic, or fluoro polymers; or hypersensitivity to contrast media that cannot be adequately premedicated.
• Subject has previously received murine therapeutic antibodies and exhibited sensitization through the production of human anti-mouse antibodies (HAMAs).
• Subject has elective surgery planned within the first 12 months after the procedure that will require interruption or discontinuation of planned Dual Antiplatelet Therapy (DAPT).
• Subject has known platelet count less than 100,000 cells/mm3 or greater than 700,000 cells/mm3, a white blood cell count of less than 3000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis).
• Subject has known renal insufficiency (eg, serum creatinine level of greater than 2.5 mg/dL or subject is on dialysis).
• Subject has history of bleeding diathesis or coagulopathy or will refuse blood transfusions.
• Subject has had a cerebrovascular accident or transient ischemic neurological attack within the past 6 months.
• Subject has had a significant gastrointestinal or urinary bleed within the past 6 months.

Sponsors & Collaborators

• OrbusNeich: lead
• OrbusNeich Medical K.K.: collaborator
• Duke Clinical Research Institute: collaborator

Study Sites (50)

MedStar Clinical Research Center

Washington D.C., District of Columbia, 20010, United States

Location

Atlantic Clinical Research Collaborative-Cardiology

Lake Worth, Florida, 33462, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

North Georgia Heart Foundation

Gainesville, Georgia, 30501, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Washington Adventist Hospital

Takoma Park, Maryland, 20912, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

North Mississippi Medical Center

Tupelo, Mississippi, 38801, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Rochester Medical Center-Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Saiseikai Fukuoka General Hospital

Fukoka-shi, Fukuoka, 810-0001, Japan

Location

Kurume University Hospital

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Shinkoga Hospital

Kurume-shi, Fukuoka, 830-8577, Japan

Location

Tsuchiya General Hospital

Hiroshima, Hiroshima, 730-655, Japan

Location

Hakodate Municipal Hospital

Hakodate-shi, Hokkaido, 041-8680, Japan

Location

Sapporo Higashi Tokushukai Hospital

Sapporo, Hokkaido, 065-0033, Japan

Location

Hyogo Brain and Heart Centre

Himeji-shi, Hyōgo, 670-0981, Japan

Location

Takahashi Hospital

Kobe, Hyōgo, 654-0026, Japan

Location

Higashi Takarazuka Satoh Hospital

Takarazukasi, Hyōgo, 665-0873, Japan

Location

Tsuchiura Kyodo Hospital

Tsuchiura, Ibaraki, 300-0053, Japan

Location

Kanazawa Cardiovascular Hospital

Kanazawa, Ishikawa-ken, 920-0007, Japan

Location

National Hospital Organisation Kagoshima Medical Centre

Kagoshima, Kagoshima-ken, 892-0583, Japan

Location

Shonan Kamakura General Hospital

Okamoto, Kamakura City, 247-8533, Japan

Location

Kanto Rosai Hospital

Kawasaki-shi, Kanagawa, 211-8510, Japan

Location

Saiseikai Yokohamashi Tobu Hospital

Yokohama, Kanagawa, 230-8765, Japan

Location

Kyoto-Katsura Hospital

Kyoto, Kyoto, 615-8256, Japan

Location

Miyazaki Medical Association Hospital

Miyazaki, Miyazaki, 880-0834, Japan

Location

Kurashiki Central Hospital

Kurashiki-shi, Okayama-ken, 710-8602, Japan

Location

The Sakakibara Heart Institute of Okayama

Okayama, Okayama-ken, 700-0804, Japan

Location

Sakurabashi Watanabe Hospital

Osaka, Osaka, 530-0001, Japan

Location

Osaka Saiseikai Nakatsu Hospital

Osaka, Osaka, 530-0012, Japan

Location

Saga University Hospital

Saga, Saga-ken, 849-8501, Japan

Location

Saitama Prefectural Cardiovascular and Respiratory Disease Centre

Kumagaya-shi, Saitama, 360-0197, Japan

Location

Okamura Memorial Hospital

Suntou-gun, Shizouka, 411-0904, Japan

Location

Jichi Medical University Hospital

Shimotsuke-shi, Tochigi, 329-0498, Japan

Location

Department of Cardiovascular Medicine, Juntendo University School of Medicine

Bunkyo-ku, Tokyo, 113-8421, Japan

Location

Sakakibara Memorial Hospital

Fuchu-shi, Tokyo, 183-0003, Japan

Location

Teikyo University Hospital

Itabashi-ku, Tokyo, 173-8606, Japan

Location

Toho University Ohashi Hospital

Meguro-ku, Tokyo, 153-8515, Japan

Location

The Cardiovascular Institute Hospital

Minato-ku, Tokyo, 106-0031, Japan

Location

Showa University Hospital

Shinagawa-ku, Tokyo, 142-8666, Japan

Location

Cardiac Catheterisation Laboratory, Keio University School of Medicine

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo, 162-8666, Japan

Location

Related Publications (2)

• Kong DF, Saito S, Nakamura S, Mehran R, Rowland SM, Handler A, Al-Khalidi HR, Krucoff MW. Rationale and design of the Japan-USA harmonized assessment by randomized, multicenter study of OrbusNEich's combo StEnt (Japan-USA HARMONEE): Assessment of a novel DES platform for percutaneous coronary revascularization in patients with ischemic coronary disease and non-ST-elevation acute coronary syndrome. Am Heart J. 2017 May;187:112-121. doi: 10.1016/j.ahj.2017.02.004. Epub 2017 Feb 12.

  PMID: 28454795 BACKGROUND

• Saito S, Krucoff MW, Nakamura S, Mehran R, Maehara A, Al-Khalidi HR, Rowland SM, Tasissa G, Morrell D, Joseph D, Okaniwa Y, Shibata Y, Bertolet BD, Rothenberg MD, Genereux P, Bezerra H, Kong DF. Japan-United States of America Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (Japan-USA HARMONEE) study: primary results of the pivotal registration study of combined endothelial progenitor cell capture and drug-eluting stent in patients with ischaemic coronary disease and non-ST-elevation acute coronary syndrome. Eur Heart J. 2018 Jul 7;39(26):2460-2468. doi: 10.1093/eurheartj/ehy275.

  PMID: 29931092 RESULT

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Debbie Morrell, Clinical Research Manager
• Organization: OrbusNeich

DMorrell@OrbusNeich.com

954-730-0711

Study Officials

• Mitchell W Krucoff, MD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

• Shigeru Saito, MD

  Shonan Kamakura General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 27, 2014
• Study Start: February 1, 2014
• Primary Completion: July 14, 2017
• Study Completion: December 1, 2021
• Last Updated: May 13, 2022
• Results First Posted: November 21, 2018

Record last verified: 2022-04

Locations

US (17); JP (33)