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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by OrbusNeich
Sponsor:
Collaborators:
OrbusNeich Medical K.K.
Duke Clinical Research Institute
Information provided by (Responsible Party):
OrbusNeich
ClinicalTrials.gov Identifier:
NCT02073565
First received: February 13, 2014
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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 EES as the active-control arm.


Condition Intervention Phase
Coronary Arteriosclerosis
Non ST Segment Elevation Acute Coronary Syndrome
Device: OrbusNeich Combo stent™
Device: Everolimus Eluting Stent (EES)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by OrbusNeich:

Primary Outcome Measures:
  • The primary clinical endpoint is Target Vessel Failure (TVF) [ Time Frame: 1 year follow-up ] [ Designated as safety issue: Yes ]
    The primary clinical endpoint of TVF, defined as cardiac death, target-vessel MI, or ischemia-driven TVR by percutaneous or surgical methods, at 1 year. Primary endpoints will be reported after all subjects have completed 12 months of follow-up. A total of 572 subjects are enrolled to ensure that 542 subjects are evaluable for the primary clinical endpoint, across all cohorts.


Secondary Outcome Measures:
  • Secondary efficacy endpoint is mechanistic OCT healthy level of intimal tissue coverage [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The secondary efficacy endpoint is mechanistic OCT healthy level of intimal tissue coverage, determined by the OCT core laboratory at 1 year for subjects in Cohorts A and B combined (total N=140 subjects).


Other Outcome Measures:
  • Additional prespecified endpoints include clinically and functionally ischemia-driven TLR [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Additional prespecified endpoints include clinically and functionally ischemia-driven TLR, including use of target-vessel FFR, analyzed dichotomously using the Fractional Flow Reserve (FFR) vs. Angiography in Multivessel Evaluation (FAME) study criteria of 0.8 during a 2 minute infusion of adenosine or adenosine triphosphate.34 Abnormal FFR-driven interventions at 1 year will be included in the evaluation of ischemia-driven TLR.

  • Human antimurine antibody (HAMA) [ Time Frame: Day of device implantation, 30 days, 12 months ] [ Designated as safety issue: No ]
    Serum will be assessed for HAMA development at index, 30 days, and 12 months in Cohort B subjects. Human antimurine antibody plasma assessment will be with blood draws performed during index procedure, 30 day follow-up visit, and 1 year catheterizations.


Estimated Enrollment: 572
Study Start Date: February 2014
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combo
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™
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.
Active Comparator: Everolimus Eluting Stent (EES)
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)
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.

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 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 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 DES study ever performed in Japan
  • Enriched population, including stabilized non-STEMI (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, WG 1, including concomitant enrollment in U.S.A. sites as an FDA-approved 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 TVR analysis
  • Mechanistic 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.
  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

To be eligible for this trial, subjects must meet all of the following criteria:

  1. 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.
  2. Subject must be at least 20 years of age at the time of randomization.
  3. Subject must have clinical or functional evidence of myocardial ischemia (eg, stable or unstable angina, stabilized non-ST-elevation MI confirmed by serum markers, ischemia by positive functional study, abnormal FFR, or a reversible change in the electrocardiogram [ECG] consistent with ischemia).
  4. Subject must be acceptable candidate with anatomy suitable for PCI with a DES.
  5. 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).
  6. Subject is an acceptable candidate for CABG surgery.

    Angiographic Anatomy Criteria—

  7. 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.
  8. 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).
  9. 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.
  10. 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 TIMI flow of 1 or greater.
  11. 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.
  12. 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.

Exclusion Criteria

If a subject meets any of the following criteria, he or she may not be enrolled in the study:

  1. STEMI at index presentation or within 7 days of study screening.
  2. 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.).
  3. Subject has known left ventricular ejection fraction (LVEF) less than 30%.
  4. Subject has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant.
  5. Subject is receiving or scheduled to receive anticancer therapy for malignancy within 30 days before or after the procedure.
  6. 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).
  7. 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.
  8. Subject has previously received murine therapeutic antibodies and exhibited sensitization through the production of HAMAs.
  9. Subject has elective surgery planned within the first 12 months after the procedure that will require interruption or discontinuation of planned DAPT.
  10. 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).
  11. Subject has known renal insufficiency (eg, serum creatinine level of greater than 2.5 mg/dL or subject is on dialysis).
  12. Subject has history of bleeding diathesis or coagulopathy or will refuse blood transfusions.
  13. Subject has had a cerebrovascular accident or transient ischemic neurological attack within the past 6 months.
  14. Subject has had a significant gastrointestinal or urinary bleed within the past 6 months.
  15. Subject has known extensive peripheral vascular disease that precludes safe 6 French sheath insertion.
  16. 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.
  17. Currently participating in another clinical study that has not yet reached its primary endpoint.
  18. 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:

  19. Unprotected left main coronary artery location.
  20. Unprotected ostial (located within 2 mm of the origin) left anterior descending artery or left circumflex.
  21. 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%).
  22. Involves a bifurcation in which the side branch is 2 mm or greater in diameter AND would be covered by the planned stent.
  23. Involves a side branch requiring predilation.
  24. Total occlusion (TIMI flow 0) before wire crossing.
  25. Extreme tortuosity proximal to or within the lesion.
  26. Extreme angulation (90º or greater) proximal to or within the lesion.
  27. 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.
  28. Restenotic vessel from previous intervention.
  29. Received brachytherapy in any epicardial vessel (including side branches).
  30. Target vessel contains angiographically visible thrombus.
  31. 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.
  32. 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.
  33. Stent overlapping is a planned treatment of the target lesion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02073565

Contacts
Contact: David F Kong, MD +1 919 668 8946 david.f.kong@duke.edu
Contact: Stephen M Rowland, PhD +1 954 343 6450 srowland@orbusneich.com

Locations
Japan
Shonan Kamakura General Hospital Recruiting
Okamoto, Kamakura City, Japan, 247-8533
Contact: Shigeru Saito, MD    +81 467 461 717 ext 10490    transradial@kamakuraheart.org   
Contact: Kazuki Tobita, MD         
Principal Investigator: Shigeru Saito, MD         
Principal Investigator: Kazuki Tobita, MD         
Sponsors and Collaborators
OrbusNeich
OrbusNeich Medical K.K.
Duke Clinical Research Institute
Investigators
Principal Investigator: Mitchell W Krucoff, MD Duke Clinical Research Institute
Principal Investigator: Shigeru Saito, MD Shonan Kamakura General Hospital
  More Information

No publications provided

Responsible Party: OrbusNeich
ClinicalTrials.gov Identifier: NCT02073565     History of Changes
Other Study ID Numbers: VP-0601, OMKK 02
Study First Received: February 13, 2014
Last Updated: July 2, 2014
Health Authority: United States: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by OrbusNeich:
intracoronary stent
drug eluting stent
sirolimus
endothelial progenitor cells
Drug Eluting Stent

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Acute Coronary Syndrome
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014