HARMONEE - Japan-USA Harmonized Assessment by Randomized, Multi-Center Study of OrbusNEich's Combo StEnt
- Conditions
- Coronary ArteriosclerosisNon ST Segment Elevation Acute Coronary Syndrome
- Interventions
- Device: OrbusNeich Combo stent™Device: Everolimus Eluting Stent (EES)
- Registration Number
- NCT02073565
- Lead Sponsor
- OrbusNeich
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 572
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combo 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. Everolimus Eluting Stent (EES) 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Target Vessel Failure (TVF) 1 year follow-up 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.
- Secondary Outcome Measures
Name Time Method Percentage of Healthy Tissue Coverage That Was Greater Than 40 Micrometers 1 year 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.
Trial Locations
- Locations (50)
Tsuchiya General Hospital
🇯🇵Hiroshima-shi, Hiroshima, Japan
Tallahassee Research Institute
🇺🇸Tallahassee, Florida, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
The Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Lahey Clinic
🇺🇸Burlington, Massachusetts, United States
Saiseikai Fukuoka General Hospital
🇯🇵Fukoka-shi, Fukuoka, Japan
Kanazawa Cardiovascular Hospital
🇯🇵Kanazawa-shi, Ishikawa, Japan
Department of Cardiovascular Medicine, Juntendo University School of Medicine
🇯🇵Bunkyo-ku, Tokyo, Japan
Cardiac Catheterisation Laboratory, Keio University School of Medicine
🇯🇵Shinjuku-ku, Tokyo, Japan
Teikyo University Hospital
🇯🇵Itabashi-ku, Tokyo, Japan
The Cardiovascular Institute Hospital
🇯🇵Minato-ku, Tokyo, Japan
University of Miami
🇺🇸Miami, Florida, United States
Higashi Takarazuka Satoh Hospital
🇯🇵Takarazukasi, Hyogo, Japan
Kyoto-Katsura Hospital
🇯🇵Kyoto-shi, Kyoto, Japan
Sakurabashi Watanabe Hospital
🇯🇵Osaka-shi, Osaka, Japan
Osaka Saiseikai Nakatsu Hospital
🇯🇵Osaka-shi, Osaka, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-shi, Tochigi, Japan
Sakakibara Memorial Hospital
🇯🇵Fuchu-shi, Tokyo, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Showa University Hospital
🇯🇵Shinagawa-ku, Tokyo, Japan
Hyogo Brain and Heart Centre
🇯🇵Himeji-shi, Hyogo, Japan
Kurashiki Central Hospital
🇯🇵Kurashiki-shi, Okayama, Japan
National Hospital Organisation Kagoshima Medical Centre
🇯🇵Kagoshima-shi, Kagoshima, Japan
MedStar Clinical Research Center
🇺🇸Washington, District of Columbia, United States
North Mississippi Medical Center
🇺🇸Tupelo, Mississippi, United States
Shinkoga Hospital
🇯🇵Kurume-shi, Fukuoka, Japan
Kanto Rosai Hospital
🇯🇵Kawasaki-shi, Kanagawa, Japan
Toho University Ohashi Hospital
🇯🇵Meguro-ku, Tokyo, Japan
The Sakakibara Heart Institute of Okayama
🇯🇵Okayama-shi, Okayama, Japan
Saga University Hospital
🇯🇵Saga-shi, Saga, Japan
Saitama Prefectural Cardiovascular and Respiratory Disease Centre
🇯🇵Kumagaya-shi, Saitama-ken, Japan
Okamura Memorial Hospital
🇯🇵Suntou-gun, Shizouka, Japan
Atlantic Clinical Research Collaborative-Cardiology
🇺🇸Lake Worth, Florida, United States
North Georgia Heart Foundation
🇺🇸Gainesville, Georgia, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Rochester Medical Center-Strong Memorial Hospital
🇺🇸Rochester, New York, United States
Kurume University Hospital
🇯🇵Kurume-shi, Fukuoka, Japan
Hakodate Municipal Hospital
🇯🇵Hakodate-shi, Hokkaido, Japan
Sapporo Higashi Tokushukai Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Tsuchiura Kyodo Hospital
🇯🇵Tsuchiura, Ibaraki, Japan
Takahashi Hospital
🇯🇵Kobe-shi, Hyogo, Japan
Shonan Kamakura General Hospital
🇯🇵Okamoto, Kamakura City, Japan
Saiseikai Yokohamashi Tobu Hospital
🇯🇵Yokohama-shi, Kanagawa, Japan
Miyazaki Medical Association Hospital
🇯🇵Miyazaki-shi, Miyazaki, Japan
Washington Adventist Hospital
🇺🇸Takoma Park, Maryland, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States