search
Back to results

Comparison of the Angiographic Result of the Orsiro Hybrid Stent With Resolute Integrity Stent (ORIENT)

Primary Purpose

Coronary Artery Disease, Coronary Heart Disease, Stable Angina

Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Osiro Hybrid Drug-Eluting Stent
Resolute Integrity
Sponsored by
Seoul National University Bundang Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring Orsiro hybrid stent, Drug-eluting stent, Zotarolimus-eluting stent, Coronary heart disease, Cobalt chromium

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject must be at least 18 years of age.
  • Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the Orsiro Hybrid DES® or Endeavor Resolute Integrity® stent.
  • He/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.
  • Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, acute myocardial infarction, recent infarction, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia) with a coronary artery or graft vessel lesion with >50% stenosis by visual estimation or >70% stenosis irrespective of the functional status.
  • Target lesion(s) must be located in a coronary artery with estimated reference diameter of ≥ 2.5 mm and ≤ 5.0 mm.
  • Target lesion(s) must be amenable for PCI.

Exclusion Criteria:

  • The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Sirolimus, Zotarolimus, Cobalt chromium, Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Those with true anaphylaxis to prior contrast media, however, should not be enrolled.)
  • Patients who cannot maintain aspirin, plavix from the study enrollment to study completion (during 1 year).
  • Systemic (intravenous) Sirolimus or Zotarolimus use within 12 months.
  • Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
  • History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or refuses blood transfusions.
  • Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months.
  • Planned major non-cardiac surgery within the study period.
  • Patients in cardiogenic shock
  • Patients with symptomatic heart failure that preclude coronary angiography in supine position.
  • Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
  • Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.

Sites / Locations

  • Korea University Ansan Hospital
  • Chungbuk University Hospital
  • Inje University Ilsan Paik Hospital
  • Inha University Hospital
  • Jeju University Hospital
  • Seoul National University Bundang Hospital
  • Boramae Medical Center
  • Kyung Hee University Hospital at Gangdong Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Orsiro

Resolute Integrity

Arm Description

The Patient group who are treated with Osiro Hybrid Drug-Eluting Stent (Biotronik AG, Bulach, Switzeland)

The Patient group who are treated with ② Resolute Integrity zotarolimus-eluting stent (Medtronic Cardiovascular, CA, Minnesota, USA)

Outcomes

Primary Outcome Measures

Late lumen loss (in-stent)
Difference between the postprocedure and 9-month follow-up in-stent minimum lumen diameter. All QCA measurements of the target lesion will be obtained in the in-stent zone, and over entire segment including the stent and its 5 mm proximal and distal margins (in-segment zone).

Secondary Outcome Measures

All-cause death
All-cause mortality at 12 months follow-up
Cardiac death
Cardiac death at 12 months follow-up. Any death due to proximate cardiac cause (eg, MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure-related deaths, including those related to concomitant treatment, will be classified as cardiac death.
Target lesion revascularization
Any target lesion revascularization (TLR), defined as repeat revascularization within the stented segment including 5 mm proximal and distal border zones. TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLRs should be classified prospectively as clinically indicated* or not clinically indicated by the investigator prior to repeat angiography. An independent angiographic core laboratory should verify that the severity of percent diameter stenosis meets requirements for clinical indication and will overrule in cases where investigator reports are not in agreement. The target lesion is defined as the treated segment from 5 mm proximal to the stent and to 5 mm distal to the stent.
Target vessel revascularization
Target vessel revascularization, defined as any revascularization of treated vessel. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion, which includes upstream and downstream branches and the target lesion itself.
Target-vessel related myocardial infarction
Myocardial infarction (MI) was defined according to the ARC definitions and an extended historical protocol definition. Target vessel related MI is defined as MI, which developed in previously treated vessel.
Non-target vessel related myocardial infarction
Myocardial infarction (MI) was defined according to the ARC definitions and an extended historical protocol definition. Non-target vessel related myocardial infarction is defined as MI, which developed in non-target vessel.
Clinical device success
Clinical Device Success is defined as an achievement of a final residual diameter stenosis of < 30% at the in-stent segment by online quantitative angiography or visual estimation, without device failure or malfunction. A device is considered to have failed if it did not meet the requirements of the definition for clinical device success.
Clinical lesion success
Clinical Lesion Success is defined as an achievement of a final in-stent segment diameter stenosis < 30% by online QCA or visual assessment over the entire stent length, with TIMI-3 flow and no more than an NHLBI type C dissection in the analysis segment
Clinical procedure success
Clinical Procedure Success is defined as an achievement of a final in-stent segment diameter stenosis < 30% by online QCA or visual assessment over the entire intervened vessel segment, with TIMI-3 flow and no more than an NHLBI type C dissection with or without any adjunctive devices, and without the occurrence of cardiac death, target vessel MI (Q-wave and non Q-wave MI), or repeat revascularization of the target lesion during the health care facility stay.
Stent thrombosis
ARC definition of stent thrombosis is classified and defined as follows. Definite/Confirmed stent thrombosis refers angiographic or pathologic confirmation of partial or total thrombotic occlusion within the per-stent region with either i) acute ischemic symptoms, ii) ischemic EKG changes, iii) elevated cardiac biomarkers. Probable stent thrombosis is defined as any unexplained death within 30 days of stent implantation or any myocardial infarction, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause. Possible stent thrombosis is defined as any unexplained death beyond 30 days of stent implantation.
Target lesion failure
Target lesion failure defined as a composite of cardiac death, myocardial infarction (not clearly attributed to a nontarget vessel), or clinically indicated target lesion revascularization by percutaneous or surgical methods at 1 years.
Patient-oriented composite outcome
Patient-oriented composite outcome included all-cause mortality, any MI (including nontarget vessel territory), and any revascularization (including all target and nontarget vessels, regardless of percutaneous or surgical methods).
In-stent/in-segment % diameter stenosis
Percent diameter stenosis in the in-stent and in-segment zone. All QCA measurements of the target lesion will be obtained in the in-stent zone, and over entire segment including the stent and its 5 mm proximal and distal margins (in-segment zone).
In-stent/in-segment binary restenosis
Binary restenosis is defined as stenosis of 50% or more at follow-up angiography). All QCA measurements of the target lesion will be obtained in the in-stent zone, and over entire segment including the stent and its 5 mm proximal and distal margins (in-segment zone).
Clinically driven revascularization
Clinically driven revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis ≥ 50% (core laboratory quantitative coronary angiography assessment) and if one of the following occurs: (1) A positive history of recurrent angina pectoris, presumably related to the target vessel; (2) Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; (3) Abnormal results of any invasive functional diagnostic test (eg, Doppler flow velocity reserve, fractional flow reserve); (4) A TLR or TVR with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms.
Late lumen loss (in-segment)
Difference between the postprocedure and 9-month follow-up in-segment minimum lumen diameter.

Full Information

First Posted
March 3, 2013
Last Updated
April 19, 2016
Sponsor
Seoul National University Bundang Hospital
Collaborators
Jeju National University Hospital, Chungbuk National University Hospital, SMG-SNU Boramae Medical Center, Korea University, Inje University, Kyung Hee University Hospital at Gangdong, Inha University Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT01826552
Brief Title
Comparison of the Angiographic Result of the Orsiro Hybrid Stent With Resolute Integrity Stent
Acronym
ORIENT
Official Title
Multicenter, Randomized, Open Label, Parallel Group Study to Evaluate the Safety and Efficacy of Orsiro Hybrid Drug Eluting Stent
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Bundang Hospital
Collaborators
Jeju National University Hospital, Chungbuk National University Hospital, SMG-SNU Boramae Medical Center, Korea University, Inje University, Kyung Hee University Hospital at Gangdong, Inha University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this multicenter, randomized, open label, parallel arm study whether the newest 3rd generation stent - Orsiro hybrid sirolimus-eluting stent is noninferior to the newest 2nd generation stent - Resolute Integrity zotarolimus-eluting stent in terms of 9 months in-stent late lumen loss. 345 Korean patients with a wide variety of coronary heart disease will be enrolled to this "all-comers" trial to give definite answer to the above hypothesis that is urgently needed.
Detailed Description
The rate of restenosis after percutaneous coronary intervention (PCI) has dramatically decreased since the introduction of drug-eluting stents (DES). However, restenosis still remains a problem and some papers reported that the rate of restenosis can even go up to nearly 20% after the first-generation DES implantation, depending on the complexity of target lesion. Furthermore, there arises a concern about thrombogenic risk of these DES at the expense of reduced restenosis. Therefore, works aiming to reduce both restenosis and thrombosis are on-going, and there has been a rush of various second-generation DES with "biocompatible but non-absorbable polymer" and third-generation DES with "bioabsorbable polymer". Recently, Orsiro hybrid sirolimus-eluting stent (Orsiro SES, Biotronik AG, Bulach, Switzeland) has been developed. It has a unique hybrid combination of polymers coated on thin cobalt-chromium struts (60um). The BIOlute® active component is a bioabsorbable polymer matrix combined with an anti-proliferative drug, sirolimus, and elutes the drug in a controlled manner after implantation, degrades over time and leaves only the PROBIO® coated stent behind in the long-term. The PROBIO® passive coating encapsulates the stent and protects interaction between the metal stent and the surrounding tissue. Although Orsiro SES showed excellent results in terms of late lumen loss at 9 months in first-in-man single arm trial (BIOFLOW-I trial), randomized controlled trials evaluating its efficacy and safety are limited to date. The ORIENT Trial will evaluate the angiographic and clinical outcomes of the innovative third-generation DES, Orsiro SES, compared with the latest second-generation DES, Resolute Integrity zotarolimus-eluting stent (ZES-I, Medtronic Cardiovascular, Santa Rosa, California, USA), for treatment of patients with coronary artery disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Coronary Heart Disease, Stable Angina, Unstable Angina, ST-segment Elevation Myocardial Infarction, Non-ST-segment Elevation Myocardial Infarction
Keywords
Orsiro hybrid stent, Drug-eluting stent, Zotarolimus-eluting stent, Coronary heart disease, Cobalt chromium

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
372 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Orsiro
Arm Type
Experimental
Arm Description
The Patient group who are treated with Osiro Hybrid Drug-Eluting Stent (Biotronik AG, Bulach, Switzeland)
Arm Title
Resolute Integrity
Arm Type
Active Comparator
Arm Description
The Patient group who are treated with ② Resolute Integrity zotarolimus-eluting stent (Medtronic Cardiovascular, CA, Minnesota, USA)
Intervention Type
Device
Intervention Name(s)
Osiro Hybrid Drug-Eluting Stent
Intervention Description
Osiro Hybrid Drug-Eluting Stent (Biotronik AG, Bulach, Switzeland)
Intervention Type
Device
Intervention Name(s)
Resolute Integrity
Intervention Description
Resolute Integrity zotarolimus-eluting stent (Medtronic Cardiovascular, CA, Minnesota, USA)
Primary Outcome Measure Information:
Title
Late lumen loss (in-stent)
Description
Difference between the postprocedure and 9-month follow-up in-stent minimum lumen diameter. All QCA measurements of the target lesion will be obtained in the in-stent zone, and over entire segment including the stent and its 5 mm proximal and distal margins (in-segment zone).
Time Frame
at 9 months
Secondary Outcome Measure Information:
Title
All-cause death
Description
All-cause mortality at 12 months follow-up
Time Frame
at 12 months
Title
Cardiac death
Description
Cardiac death at 12 months follow-up. Any death due to proximate cardiac cause (eg, MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure-related deaths, including those related to concomitant treatment, will be classified as cardiac death.
Time Frame
at 12 months
Title
Target lesion revascularization
Description
Any target lesion revascularization (TLR), defined as repeat revascularization within the stented segment including 5 mm proximal and distal border zones. TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLRs should be classified prospectively as clinically indicated* or not clinically indicated by the investigator prior to repeat angiography. An independent angiographic core laboratory should verify that the severity of percent diameter stenosis meets requirements for clinical indication and will overrule in cases where investigator reports are not in agreement. The target lesion is defined as the treated segment from 5 mm proximal to the stent and to 5 mm distal to the stent.
Time Frame
at 12 months
Title
Target vessel revascularization
Description
Target vessel revascularization, defined as any revascularization of treated vessel. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion, which includes upstream and downstream branches and the target lesion itself.
Time Frame
at 12 months
Title
Target-vessel related myocardial infarction
Description
Myocardial infarction (MI) was defined according to the ARC definitions and an extended historical protocol definition. Target vessel related MI is defined as MI, which developed in previously treated vessel.
Time Frame
at 12 months
Title
Non-target vessel related myocardial infarction
Description
Myocardial infarction (MI) was defined according to the ARC definitions and an extended historical protocol definition. Non-target vessel related myocardial infarction is defined as MI, which developed in non-target vessel.
Time Frame
at 12 months
Title
Clinical device success
Description
Clinical Device Success is defined as an achievement of a final residual diameter stenosis of < 30% at the in-stent segment by online quantitative angiography or visual estimation, without device failure or malfunction. A device is considered to have failed if it did not meet the requirements of the definition for clinical device success.
Time Frame
Baseline
Title
Clinical lesion success
Description
Clinical Lesion Success is defined as an achievement of a final in-stent segment diameter stenosis < 30% by online QCA or visual assessment over the entire stent length, with TIMI-3 flow and no more than an NHLBI type C dissection in the analysis segment
Time Frame
Baseline
Title
Clinical procedure success
Description
Clinical Procedure Success is defined as an achievement of a final in-stent segment diameter stenosis < 30% by online QCA or visual assessment over the entire intervened vessel segment, with TIMI-3 flow and no more than an NHLBI type C dissection with or without any adjunctive devices, and without the occurrence of cardiac death, target vessel MI (Q-wave and non Q-wave MI), or repeat revascularization of the target lesion during the health care facility stay.
Time Frame
Baseline
Title
Stent thrombosis
Description
ARC definition of stent thrombosis is classified and defined as follows. Definite/Confirmed stent thrombosis refers angiographic or pathologic confirmation of partial or total thrombotic occlusion within the per-stent region with either i) acute ischemic symptoms, ii) ischemic EKG changes, iii) elevated cardiac biomarkers. Probable stent thrombosis is defined as any unexplained death within 30 days of stent implantation or any myocardial infarction, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause. Possible stent thrombosis is defined as any unexplained death beyond 30 days of stent implantation.
Time Frame
at 12 months
Title
Target lesion failure
Description
Target lesion failure defined as a composite of cardiac death, myocardial infarction (not clearly attributed to a nontarget vessel), or clinically indicated target lesion revascularization by percutaneous or surgical methods at 1 years.
Time Frame
at 12 months
Title
Patient-oriented composite outcome
Description
Patient-oriented composite outcome included all-cause mortality, any MI (including nontarget vessel territory), and any revascularization (including all target and nontarget vessels, regardless of percutaneous or surgical methods).
Time Frame
at 12 months
Title
In-stent/in-segment % diameter stenosis
Description
Percent diameter stenosis in the in-stent and in-segment zone. All QCA measurements of the target lesion will be obtained in the in-stent zone, and over entire segment including the stent and its 5 mm proximal and distal margins (in-segment zone).
Time Frame
at 9 months
Title
In-stent/in-segment binary restenosis
Description
Binary restenosis is defined as stenosis of 50% or more at follow-up angiography). All QCA measurements of the target lesion will be obtained in the in-stent zone, and over entire segment including the stent and its 5 mm proximal and distal margins (in-segment zone).
Time Frame
at 9 months
Title
Clinically driven revascularization
Description
Clinically driven revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis ≥ 50% (core laboratory quantitative coronary angiography assessment) and if one of the following occurs: (1) A positive history of recurrent angina pectoris, presumably related to the target vessel; (2) Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; (3) Abnormal results of any invasive functional diagnostic test (eg, Doppler flow velocity reserve, fractional flow reserve); (4) A TLR or TVR with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms.
Time Frame
at 12 months
Title
Late lumen loss (in-segment)
Description
Difference between the postprocedure and 9-month follow-up in-segment minimum lumen diameter.
Time Frame
at 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must be at least 18 years of age. Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the Orsiro Hybrid DES® or Endeavor Resolute Integrity® stent. He/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, acute myocardial infarction, recent infarction, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia) with a coronary artery or graft vessel lesion with >50% stenosis by visual estimation or >70% stenosis irrespective of the functional status. Target lesion(s) must be located in a coronary artery with estimated reference diameter of ≥ 2.5 mm and ≤ 5.0 mm. Target lesion(s) must be amenable for PCI. Exclusion Criteria: The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Sirolimus, Zotarolimus, Cobalt chromium, Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Those with true anaphylaxis to prior contrast media, however, should not be enrolled.) Patients who cannot maintain aspirin, plavix from the study enrollment to study completion (during 1 year). Systemic (intravenous) Sirolimus or Zotarolimus use within 12 months. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or refuses blood transfusions. Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months. Planned major non-cardiac surgery within the study period. Patients in cardiogenic shock Patients with symptomatic heart failure that preclude coronary angiography in supine position. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment). Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tae-Jin Youn, MD,PhD
Organizational Affiliation
Division of Cardiology, Department of Internal Medicine, College of Medicine, Seoul National University and Cardiovascular Center, Seoul National University Bundang Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dong-Ju Choi, MD,PhD
Organizational Affiliation
Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Seoul National University Bundang Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
In-Ho Chae, MD,PhD
Organizational Affiliation
Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Seoul National University Bundang Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Korea University Ansan Hospital
City
Ansan
Country
Korea, Republic of
Facility Name
Chungbuk University Hospital
City
Cheongju
Country
Korea, Republic of
Facility Name
Inje University Ilsan Paik Hospital
City
Ilsan
Country
Korea, Republic of
Facility Name
Inha University Hospital
City
Incheon
Country
Korea, Republic of
Facility Name
Jeju University Hospital
City
Jeju
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
Country
Korea, Republic of
Facility Name
Boramae Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Kyung Hee University Hospital at Gangdong Hospital
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
24257456
Citation
Lee JM, Park SD, Lim SY, Doh JH, Cho JM, Kim KS, Bae JW, Chung WY, Youn TJ. Angiographic and clinical comparison of novel Orsiro Hybrid sirolimus-eluting stents and Resolute Integrity zotarolimus-eluting stents in all-comers with coronary artery disease (ORIENT trial): study protocol for a randomized controlled trial. Trials. 2013 Nov 20;14:398. doi: 10.1186/1745-6215-14-398.
Results Reference
derived

Learn more about this trial

Comparison of the Angiographic Result of the Orsiro Hybrid Stent With Resolute Integrity Stent

We'll reach out to this number within 24 hrs