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Coronary ArteriosclerosisHARMONEENCT02073565

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

A study testing OrbusNeich Combo stent™ and Everolimus Eluting Stent (EES) in people with Coronary Arteriosclerosis and Non ST Segment Elevation Acute Coronary Syndrome, run by OrbusNeich at 50 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
OrbusNeich Combo stent™ and Everolimus Eluting Stent (EES)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
572 participants
Where
50 sitesin 2 countries
Study dates
Feb 2014to Dec 2021
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 14Show fewer
  • 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.

Who cannot join

  • 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.
Show all 36Show fewer
  • 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.
  • Subject has known extensive peripheral vascular disease that precludes safe 6 French sheath insertion.
  • Known other medical illness (eg, cancer, chronic infectious disease, severe vascular disease, or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that may cause noncompliance with the protocol, confound the data interpretation, or is associated with a life expectancy of less than 1 year.
  • Currently participating in another clinical study that has not yet reached its primary endpoint.
  • Currently pregnant or breast-feeding or is planning pregnancy in the period up to 1 year following index procedure. Female subjects of childbearing potential must have a negative pregnancy test within 7 days before the index procedure.
  • Angiographic Exclusion Criteria-
  • If the target lesion meets any of the following criteria, the subject may not be enrolled in the study:
  • Unprotected left main coronary artery location.
  • Unprotected ostial (located within 2 mm of the origin) left anterior descending artery or left circumflex.
  • Located within an arterial or saphenous vein graft or graft anastomosis, distal to a diseased arterial or saphenous vein graft (visually estimated graft diameter stenosis greater than 40%).
  • Involves a bifurcation in which the side branch is 2 mm or greater in diameter AND would be covered by the planned stent.
  • Involves a side branch requiring predilation.
  • Total occlusion (TIMI flow 0) before wire crossing.
  • Extreme tortuosity proximal to or within the lesion.
  • Extreme angulation (90º or greater) proximal to or within the lesion.
  • Heavy calcification, defined as multiple persisting opacifications of the coronary wall visible in more than one projection surrounding the complete lumen of the coronary artery at the site of the lesion.
  • Restenotic vessel from previous intervention.
  • Received brachytherapy in any epicardial vessel (including side branches).
  • Target vessel contains angiographically visible thrombus.
  • Serial lesions or diffuse disease with high probability of bailout requiring 3 or more stents in a single vessel, more than 5 stents per subject, or more than 2 vessels.
  • Target or nontarget vessel lesion (including all side branches) is present with a high probability of requiring PCI within 12 months after the index procedure.
  • Stent overlapping is a planned treatment of the target lesion.

Trial locations and contacts

50 sites in 2 countries.

50 sites in 2 countries

Japan33 sites

  • Department of Cardiovascular Medicine, Juntendo University School of Medicine

    Bunkyo-ku, Tokyo, 113-8421

  • Sakakibara Memorial Hospital

    Fuchu-shi, Tokyo, 183-0003

  • Saiseikai Fukuoka General Hospital

    Fukoka-shi, Fukuoka, 810-0001

  • Hakodate Municipal Hospital

    Hakodate-shi, Hokkaido, 041-8680

  • Hyogo Brain and Heart Centre

    Himeji-shi, Hyōgo, 670-0981

  • Tsuchiya General Hospital

    Hiroshima, Hiroshima, 730-655

  • Teikyo University Hospital

    Itabashi-ku, Tokyo, 173-8606

  • National Hospital Organisation Kagoshima Medical Centre

    Kagoshima, Kagoshima-ken, 892-0583

  • Kanazawa Cardiovascular Hospital

    Kanazawa, Ishikawa-ken, 920-0007

  • Kanto Rosai Hospital

    Kawasaki-shi, Kanagawa, 211-8510

  • Takahashi Hospital

    Kobe, Hyōgo, 654-0026

  • Saitama Prefectural Cardiovascular and Respiratory Disease Centre

    Kumagaya-shi, Saitama, 360-0197

  • Kurashiki Central Hospital

    Kurashiki-shi, Okayama-ken, 710-8602

  • Kurume University Hospital

    Kurume-shi, Fukuoka, 830-0011

  • Shinkoga Hospital

    Kurume-shi, Fukuoka, 830-8577

  • Kyoto-Katsura Hospital

    Kyoto, Kyoto, 615-8256

  • Toho University Ohashi Hospital

    Meguro-ku, Tokyo, 153-8515

  • The Cardiovascular Institute Hospital

    Minato-ku, Tokyo, 106-0031

  • Miyazaki Medical Association Hospital

    Miyazaki, Miyazaki, 880-0834

  • Shonan Kamakura General Hospital

    Okamoto, Kamakura City, 247-8533

  • The Sakakibara Heart Institute of Okayama

    Okayama, Okayama-ken, 700-0804

  • Sakurabashi Watanabe Hospital

    Osaka, Osaka, 530-0001

  • Osaka Saiseikai Nakatsu Hospital

    Osaka, Osaka, 530-0012

  • Saga University Hospital

    Saga, Saga-ken, 849-8501

  • Sapporo Higashi Tokushukai Hospital

    Sapporo, Hokkaido, 065-0033

  • Jichi Medical University Hospital

    Shimotsuke-shi, Tochigi, 329-0498

  • Showa University Hospital

    Shinagawa-ku, Tokyo, 142-8666

  • Cardiac Catheterisation Laboratory, Keio University School of Medicine

    Shinjuku-ku, Tokyo, 160-8582

  • Tokyo Women's Medical University Hospital

    Shinjuku-ku, Tokyo, 162-8666

  • Okamura Memorial Hospital

    Suntou-gun, Shizouka, 411-0904

  • Higashi Takarazuka Satoh Hospital

    Takarazukasi, Hyōgo, 665-0873

  • Tsuchiura Kyodo Hospital

    Tsuchiura, Ibaraki, 300-0053

  • Saiseikai Yokohamashi Tobu Hospital

    Yokohama, Kanagawa, 230-8765

Other trials in Japan

United States17 sites

  • Lehigh Valley Hospital

    Allentown, Pennsylvania, 18103

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • The Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • North Georgia Heart Foundation

    Gainesville, Georgia, 30501

  • Atlantic Clinical Research Collaborative-Cardiology

    Lake Worth, Florida, 33462

  • University of Miami

    Miami, Florida, 33136

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Maine Medical Center

    Portland, Maine, 04102

  • University of Rochester Medical Center-Strong Memorial Hospital

    Rochester, New York, 14642

  • Washington Adventist Hospital

    Takoma Park, Maryland, 20912

  • Tallahassee Research Institute

    Tallahassee, Florida, 32308

  • North Mississippi Medical Center

    Tupelo, Mississippi, 38801

  • MedStar Clinical Research Center

    Washington D.C., District of Columbia, 20010

  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Japan-USA Harmonized Assessment by Randomized, Multi-Center 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 NSTEMI Acute Coronary Syndrome

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.

Read the detailed description

Up to 50 sites are proposed in Japan and the United States to enroll 286 subjects (271 evaluable) in each of 2 arms, for a total sample size of 572 subjects (542 evaluable) who are admitted to the hospital for a planned (elective and urgent) percutaneous coronary artery intervention procedure.

After stent implantation, subjects will be contacted for follow-up at 30 days; 6 months; and 1, 2, 3, 4, and 5 years. At 12 months a clinical evaluation will be completed before cardiac catheterization and angiographic assessment.

Rationale: This study is intended to demonstrate that the Combo stent platform shows superiority to an imputed Bare Metal Stent (BMS) performance goal, noninferior effectiveness and safety vs best-in-class second-generation everolimus-eluting stent (EES) (Xience V, Xience Prime, Xience Xpedition stents; [Abbott Vascular/Abbott Vascular Japan]), and evidence of mechanistic activity of the anti-CD34-Ab endothelial progenitor cell (EPC) capture technology with healthy level of intimal tissue coverage superior to that of the best-in-class EES.

To ensure the robustness and interpretability of results, the current proposal includes a number of unique design features:

  • Largest randomized Drug-Eluting Stent (DES) study ever performed in Japan
  • Enriched population, including stabilized Non-ST-elevation myocardial infarction (NSTEMI) subjects with greater likelihood of plaque rupture associated with their clinical syndromes
  • Collaboration between with Japan and the United States as a "Proof of Concept" program under the auspices of the Harmonization by Doing Initiative, Working Group 1 (WG 1), including concomitant enrollment in U.S.A. sites as an FDA-approved Investigational Device Exemption (IDE) study
  • Head-to-head randomization against state-of-the-art EES platform control, analyzed for clinical noninferiority
  • Statistical analysis vs imputed BMS analyzed for clinical superiority
  • Fractional flow reserve (FFR) follow-up of 100% of subjects enrolled, providing clinically relevant physiologic assessment of all subjects for 1 year ischemia-driven Target Vessel Revascularization (TVR) analysis
  • Mechanistic Optical coherence tomography (OCT) imaging observations in 140 subjects using 6 French catheters as follows:
  • Cohort A (30 subjects, 1:1 Combo and EES): Mechanistic imaging observations to provide serial 6 month and 1 year OCT evaluation of healthy intimal tissue coverage, intracoronary thrombosis, and stent malapposition and quantitative coronary angiographic (QCA) analysis to assess 1 year late loss.
  • Cohort B (110 subjects, 1:1 Combo and EES): Mechanistic imaging observations to assess 1 year OCT evaluation of healthy intimal tissue coverage, intracoronary thrombosis, and stent malapposition, and QCA analysis to assess 1 year late loss. Combined with the 12 month imaging of Cohort A, this study will provide OCT and QCA observations at 1 year in 140 patients, half with Combo and half with EES.
  • Cohort C: 432 subjects (216 subjects per arm) will undergo all clinical follow-up assessments with FFR and angiographic assessments at 12 months. Cohort C will be the last cohort to enroll.
  • In the 110 subjects in Cohort B, 30 day and 1 year human antimurine antibody (HAMA) titers will also be collected.
Being tested
OrbusNeich Combo stent™, Everolimus Eluting Stent (EES)
Keywords
intracoronary stent, drug eluting stent, sirolimus, endothelial progenitor cells
Medical subject headings
Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • 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.

Study groups in NCT02073565
Study groupRoleWhat they receive
ComboExperimentalThe 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.
Receives: Device: OrbusNeich Combo stent™
Everolimus Eluting Stent (EES)Active comparatorEverolimus 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.
Receives: Device: Everolimus Eluting Stent (EES)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year follow-up

Secondary outcomes (1)

  1. Percentage of Healthy Tissue Coverage That Was Greater Than 40 Micrometers

    The secondary efficacy endpoint is mechanistic Optical coherence tomography (OCT) healthy level of intimal tissue coverage, determined by the OCT core laboratory at 1 year for subjects in Cohorts A and B. This reports the percentage of healthy tissue coverage that was great than 40 micrometers.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completion14 Jul 2017
  4. Study completionDec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
572 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02073565
Sponsor's protocol ID
VP-0601
Other IDs
OMKK 02
Acronym
HARMONEE
Status last verified
Apr 2022
First submitted
13 Feb 2014
Last updated
13 May 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28454795

  • 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.

    PubMed 29931092

Questions about this trial

What is this clinical trial studying?

A study testing OrbusNeich Combo stent™ and Everolimus Eluting Stent (EES) in people with Coronary Arteriosclerosis and Non ST Segment Elevation Acute Coronary Syndrome, run by OrbusNeich at 50 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in Japan, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Target Vessel Failure (TVF) (time frame: 1 year follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02073565, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2022.

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