Optimal Duration of DAPT Following Treatment With Endeavor (Zotarolimus-eluting Stent) in Real-world Japanese Patients (OPERA)

Optimal Duration of DAPT Following Treatment With Endeavor (Zotarolimus-eluting Stent) in Real-world Japanese Patients: A Prospective Multicenter Registry (OPERA)

A prospective multicenter registry in real-world Japanese patients undergoing DAPT for three months after stenting. To assess the long-term safety of Endeavor Zotarolimus-eluting stent through noninferiority in the primary endpoint between two different continuous regimen (three and twelve months) groups of DAPT after stenting with Endeavor Zotarolimus-eluting stent in real-world Japanese patients and to examine the optimal duration of DAPT after stenting with Endeavor Zotarolimus-eluting stent. The long-term DAPT group in the present clinical study (to be appropriated from the post-marketing surveillance of Endeavor) should consist of consecutive patients undergoing DAPT for twelve months after stenting, while the short-term DAPT group (to be newly registered in the present clinical study) should consist of patients who are instructed to undergo DAPT for three months after stenting.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Actual): 1187
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Minato-ku, Tokyo, Japan, 105-0013
    • Non-profit organization Associations for Establishiment of Evidence in Interventions
  • Chiba
    • Asahi City, Chiba, Japan
      • Asahi General Hospital
    • Kisarazu City, Chiba, Japan
      • Kimitsu Chuo Hospital
  • Fukui
    • Fukui City, Fukui, Japan
      • Fukui Cardiovascular Center
  • Fukuoka
    • Fukuoka City, Fukuoka, Japan
      • Fukuoka City Hospital
    • Fukuoka City, Fukuoka, Japan
      • Fukuoka City Medical Association Hospital
    • Fukuoka City, Fukuoka, Japan
      • Fukuoka Red Cross Hospital
    • Kita-Kyushu City, Fukuoka, Japan
      • University of Occupational and Environmental Health
    • Koga City, Fukuoka, Japan
      • National Hospital Organization Fukuoka-Higashi Medical Center
  • Gifu
    • Gifu City, Gifu, Japan
      • Gifu Heart Center
  • Hiroshima
    • Fukuyama City, Hiroshima, Japan
      • Fukuyama City Hospital
    • Hiroshima City, Hiroshima, Japan
      • Hiroshima Railway Hospital
    • Hiroshima City, Hiroshima, Japan
      • Tsuchiya General Hospital
  • Hokkaido
    • Monbetsu-gun, Hokkaido, Japan
      • Engaru-Kosei General Hospital
  • Hyogo
    • Amagasaki City, Hyogo, Japan
      • Hyogo Prefectural Amagasaki Hospital
    • Amagasaki City, Hyogo, Japan
      • Kansai Rosai Hospital, Cardiovascular Center
    • Kobe City, Hyogo, Japan
      • Kobe City Medical Center General Hospital
    • Kobe City, Hyogo, Japan
      • Shakaihoken Kobe Central Hospital
    • Miki City, Hyogo, Japan
      • Miki City Hospital
    • Nishinomiya City, Hyogo, Japan
      • Hyogo College of Medicine
    • Nishinomiya City, Hyogo, Japan
      • Meiwa General Hospital
    • Sumoto City, Hyogo, Japan
      • Hyogo Prefectural Awaji Hospital
  • Ishikawa
    • Kanazawa City, Ishikawa, Japan
      • Kanazawa University Hospital
  • Kagawa
    • Sakaide City, Kagawa, Japan
      • Kaisei General Hospital
  • Kagoshima
    • Kagoshima City, Kagoshima, Japan
      • Kagoshima University Hospital
    • Kagoshima City, Kagoshima, Japan
      • Tenyoukai Central Hospital
  • Kanagawa
    • Ebina City, Kanagawa, Japan
      • Ebina General Hospital
    • Fujisawa City, Kanagawa, Japan
      • Fujisawa City Hospital
    • Kawasaki City, Kanagawa, Japan
      • Kawasaki Municipal Tama Hospital
    • Kawasaki City, Kanagawa, Japan
      • St. Marianna University of Medicine, Toyoko Hospital
    • Kawasaki City, Kanagawa, Japan
      • St. Marianna University School of Medicine
    • Kawasaki City, Kanagawa, Japan
      • Synthesis Shinkawahashi Hospital
    • Odawara City, Kanagawa, Japan
      • Odawara Cardiovascular Hospital
    • Sagamihara City, Kanagawa, Japan
      • Kitazato University School of Medicine
    • Sagamihara City, Kanagawa, Japan
      • Sagamihara Kyodo Hospital
    • Yokohama City, Kanagawa, Japan
      • Kanagawa Cardiovascular and Reppiratory Center
    • Yokohama City, Kanagawa, Japan
      • Saiseikai Yokohama tobu Hospital
    • Yokohama City, Kanagawa, Japan
      • Showa University Fujigaoka Hospital
    • Yokohama City, Kanagawa, Japan
      • St. Marianna University of Medicine, Yokohama City West Hospital
    • Yokohama City, Kanagawa, Japan
      • Yokohama City University Hospital
    • Yokohama City, Kanagawa, Japan
      • Yokohama City University Medical Center
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan
      • Kumamoto Chuo Hospital
    • Kumamoto City, Kumamoto, Japan
      • Kumamoto Red Cross Hospital
    • Kumamoto City, Kumamoto, Japan
      • National Hospital Organization Kumamoto Medical Center
    • Kumamoto City, Kumamoto, Japan
      • Saiseikai Kumamoto Hospital
    • Kumamoto City, Kumamoto, Japan
      • Sugimura Hospital
  • Kyoto
    • Kyoto City, Kyoto, Japan
      • Ijinkai Takeda General Hospital
    • Kyoto City, Kyoto, Japan
      • Koseikai Takeda Hospital
    • Kyoto City, Kyoto, Japan
      • Kyoto Second Red Cross Hospital
    • Sagara-gun, Kyoto, Japan
      • Gakken The Holy City Medical Association Hospital
    • Uji City, Kyoto, Japan
      • Uji Tokushukai Hospital
  • Mie
    • Matsuzaka City, Mie, Japan
      • Matsuzaka Central General Hospital
    • Suzuka City, Mie, Japan
      • Suzuka Central General Hospital
    • Taki-gun, Mie, Japan
      • Mie Heart Center
    • Tsu City, Mie, Japan
      • Mie University Hospital
  • Nagasaki
    • Nagasaki City, Nagasaki, Japan
      • Nagasaki University Graduate School of Biomedical Science
  • Okayama
    • Kurashiki City, Okayama, Japan
      • Kawasaki Medical School
    • Okayama City, Okayama, Japan
      • National Hospital Organization Okayama Medical Center
    • Okayama City, Okayama, Japan
      • The Sakakibara Heart Institute of Okayama
  • Okinawa
    • Naha City, Okinawa, Japan
      • Ohama Daiichi Hospital
    • Okinawa City, Okinawa, Japan
      • Nakagami Hospital
    • Shimajiri-gun, Okinawa, Japan
      • Okinawa Nanbu Tokushukai Hospital
    • Urasoe City, Okinawa, Japan
      • Urasoe General Hospital
  • Osaka
    • Higashi Osaka City, Osaka, Japan
      • Kawachi General Hospital
    • Hirakata City, Osaka, Japan
      • Kansai Medical University Hirakata Hospital
    • Moriguchi City, Osaka, Japan
      • Kansai Medical University Takii Hospital
    • Neyagawa City, Osaka, Japan
      • Komatsu General Hospital
    • Osaka City, Osaka, Japan
      • Higashi-sumiyoshi Morimoto Hospital
    • Osaka City, Osaka, Japan
      • Nissay Hospital
    • Osaka City, Osaka, Japan
      • Osaka City General Hospital
    • Osaka City, Osaka, Japan
      • Osaka City University, Graduate School of Medicine
    • Osaka City, Osaka, Japan
      • Osaka Ekisaikai Hospital
    • Osaka City, Osaka, Japan
      • Osaka General Hospital of West Japan Railway Campany
    • Osaka City, Osaka, Japan
      • Osaka General Medical Center
    • Osaka City, Osaka, Japan
      • Osaka Gyoumeikan Hospital
    • Osaka City, Osaka, Japan
      • Osaka Police Hospital
    • Osaka City, Osaka, Japan
      • SAKURABASHi WATANABE HOSPITAL
    • Sakai City, Osaka, Japan
      • Bell Land General Hospital
    • Sakai City, Osaka, Japan
      • Mimihara General Hospital
    • Suita City, Osaka, Japan
      • National Cerebral and Cardiovascular Center
    • Suita City, Osaka, Japan
      • Osaka University Graduate School of Medicine
    • Suita City, Osaka, Japan
      • Saiseikai Senri Hospital
    • Takatsuki City, Osaka, Japan
      • Hokusetsu General Hospital
    • Takatsuki City, Osaka, Japan
      • Midorigaoka Hospital
  • Saga
    • Saga City, Saga, Japan
      • Department of Cardiovascular Medicine, Saga University
  • Saitama
    • Kawaguchi City, Saitama, Japan
      • Mashiko Hospital
    • Saitama City, Saitama, Japan
      • Saitama Medical Center, Jichi Medical University
  • Shiga
    • Kusatsu City, Shiga, Japan
      • Kusatsu Heart Center
    • Moriyama City, Shiga, Japan
      • Shiga Medical Center for Adults
    • Omihachiman City, Shiga, Japan
      • Omihachiman Community Medical Center
    • Otsu City, Shiga, Japan
      • Biwako Ohashi Hospital
  • Shizuoka
    • Hamamatsu City, Shizuoka, Japan
      • Seirei Hamamatsu General Hospital
    • Hamamatsu City, Shizuoka, Japan
      • Hamamatsu Medical Center
    • Izunokuni City, Shizuoka, Japan
      • Juntendo University Shizuoka Hospital
  • Tokushima
    • Komatsujima City, Tokushima, Japan
      • Tokushima Red Cross Hospital
  • Tokyo
    • Adachi-ku, Tokyo, Japan
      • Ayase heart hospital
    • Bunkyo-ku, Tokyo, Japan
      • Juntendo University Hospital
    • Bunkyo-ku, Tokyo, Japan
      • The University of Tokyo Hospital
    • Chuo-ku, Tokyo, Japan
      • St. Luke's International Hospital
    • Fuchu City, Tokyo, Japan
      • Sakakibara Heart Institute
    • Fuchu City, Tokyo, Japan
      • Tokyo Metroporitan Tama Medical Center
    • Itabashi-ku, Tokyo, Japan
      • Teikyo University Hospital
    • Itabashi-ku, Tokyo, Japan
      • Itabashi Chuo Medical Center
    • Itabashi-ku, Tokyo, Japan
      • Nihon University School of Medicine
    • Itabashi-ku, Tokyo, Japan
      • Tokyo Metroporitan Geriatric Hospital and Institute of Gerontology
    • Meguro-ku, Tokyo, Japan
      • Toho University Medical Center Ohashi Hospital
    • Minato-ku, Tokyo, Japan
      • The Jikei University Hospital
    • Minato-ku, Tokyo, Japan
      • The Cardiovascular Institute
    • Shibuya-ku, Tokyo, Japan
      • JR Tokyo General Hospital
    • Shinagawa-ku, Tokyo, Japan
      • NTT Medical Center Tokyo
  • Tottri
    • Yonago City, Tottri, Japan
      • Tottri University
  • Yamaguchi
    • Yanai City, Yamaguchi, Japan
      • Shuto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical inclusion criteria

   • Patient over age 20 years.
   • Patient who is clinically indicated for PCI by stenting at least in one coronary lesion that is visually confirmed by coronary angiography.
   • Patient who has agreed to conditions after receiving an explanation about the contents of the present clinical study and who has signed the consent form approved by the ethical review board at each study site.
   • Patient who has agreed to undergo all clinical FUs listed in the present protocol.

2. Coronary angiographic inclusion criteria:

   • Patient who has a > 50% occlusion or stenosis that is visually confirmed by coronary angiography in a native coronary artery > 2.5 mm in diameter and in whom the relevant coronary artery has an anatomical structure that is eligible for PCI with Endeavor Zotarolimus-eluting stent.

Exclusion Criteria:

1. Clinical exclusion criteria

   • Patient over age 85 years.
   • Patient with ST elevation MI who requires primary or rescue PCI and whose performance status falls under any of the exclusion criteria.
   • Patient with cardiogenic shock.
   • Patient who underwent stent treatment with BMS in other lesions within 6 months prior to the conduct of index PCI of the target vessel.
   • Patient who has undergone some treatment with DES for coronary lesions.
   • Patient who is scheduled to undergo elective surgery within 12 months after index PCI.
   • Patient whose left ventricular ejection fraction (LVEF) is < 40%.
   • Patient with a hemorrhagic predisposition or a history of coagulation abnormality
   • Patient in whom the total number of deployed stents exceeds 4,regardless of the number of lesions and the number of affected branches.
   • Patient with a verified history of CVA before stenting.
   • Patient with a verified history of active peptic ulcer or upper gastrointestinal tract bleeding before Stenting.
   • Patient showing impaired renal function. (serum creatinine concentration: > 1.8 mg/dL)
   • Patient with known contraindications for aspirin or clopidogrel. (the physician should assess tolerability within the range of routine medical care)
   • Patient with a known disorder who has a life expectancy of less than 12 months.
   • Patient who is incompetent to adhere to all clinical FUs listed in the present protocol.

2. Angiographic exclusion criteria:

   • Lesions located within the saphenous venin graft (SVG).
   • Unprotected lesions in the left coronary trunk.
   • Lesions of in-stent restenosis in previously deployed DES or BMS.
   • Lesions with an anatomical structure of the coronary artery that is not eligible for treatment by the deployment of Endeavor ZES.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short-term DAPT group; 1,200 patients to be newly registered: Undergo 3-month (+ 30 days) DAPT (aspirin and clopidogrel)	Drug: Clopidogrel; DAPT using aspirin 81 mg/day (minimal dose) and clopidogrel 75 mg/day should be conducted for 3 months (+ 30 days) after stenting.
No Intervention: Long-term DAPT group; 1,200 patients to be appropriated from E-Japan post-marketing surveillance who meet all inclusion criteria and do not fall under any exclusion criteria of the present clinical study: Undergo 12-month DAPT (aspirin and clopidogrel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NACCE (Net adverse clinical and cerebral event)	NACCE is defined as a composite endpoint consisting of death from some causes (including cardiac death and noncardiac death), myocardial infarction (Q-wave MI and non-Q wave MI), cerebral vascular accident, and major bleeding (as per the modified version of REPLACE-2 criteria for bleeding and as per GUSTO criteria for bleeding).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stent thrombosis	Incidence of stent thrombosis as per the definition by academic research council	12 months
MACE (major adverse cardiac events)	Incidence of MACE at months 1, 3, 6, 9, and 12 after stenting. MACE is defined as a composite endpoint consisting of cardiac death from some causes (including cardiac and noncardiac death), MI (Q-wave MI and non-Q wave MI), TLR, and coronary artery bypass graft (CABG).	1, 3, 6, 9 and 12 months
TVR (target vessel revascularization)	Incidence of target vessel revascularization at months 9 and 12 after stenting.	9 and 12 months
TLR (target lesion revascularization)	Incidence of target lesion revascularization at months 9 and 12 after stenting.	9 and 12 months
DAPT compliance	Duration of DAPT and patient compliance.	12 months
Hemorrhagic complications	Incidence of hemorrhagic complications. (as per the modified version of REPLACE-2 criteria for bleeding and as per GUSTO criteria for bleeding)	12 months

Collaborators and Investigators

• Sponsor: Associations for Establishment of Evidence in Interventions
• Collaborators: Medtronic
• Investigators: Principal Investigator: Takaaki Isshiki, M.D., Teikyo University; Principal Investigator: Shinsuke Nanto, M.D., Osaka University; Principal Investigator: Masato Nakamura, M.D., Toho University Ohashi Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 29, 2011
• First Submitted That Met QC Criteria: March 29, 2011
• First Posted (Estimate): March 30, 2011

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: January 5, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Cardiovascular Disease; Vascular Disease; Heart Disease; Platelet Aggregation Inhibitors; Clopidogrel; Arteriosclerosis; Myocardial Ischemia; Coronary Disease; Arterial Occlusive Disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: OPERA 1.0 - AEEI