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

Coronary Artery Disease Clinical Trial

— ORIENT  

Official title:

Multicenter, Randomized, Open Label, Parallel Group Study to Evaluate the Safety and Efficacy of Orsiro Hybrid Drug Eluting Stent

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01826552
• Other study ID #: NCT01826552
• Status: Completed
• Phase: Phase 4
• First received: March 3, 2013
• Last updated: April 19, 2016
• Start date: September 2013
• Est. completion date: June 2015

Study information

• Verified date: April 2016
• Source: Seoul National University Bundang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 372
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina, Stable
• Angina, Unstable
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Infarction
• Myocardial Infarction
• Myocardial Ischemia
• Non-ST-segment Elevation Myocardial Infarction
• ST-segment Elevation Myocardial Infarction
• Stable Angina
• Unstable Angina

Intervention

Device:
• Osiro Hybrid Drug-Eluting Stent
Osiro Hybrid Drug-Eluting Stent (Biotronik AG, Bulach, Switzeland)
• Resolute Integrity
Resolute Integrity zotarolimus-eluting stent (Medtronic Cardiovascular, CA, Minnesota, USA)

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Chungbuk University Hospital	Cheongju
Korea, Republic of	Inje University Ilsan Paik Hospital	Ilsan
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Jeju University Hospital	Jeju
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Boramae Medical Center	Seoul
Korea, Republic of	Kyung Hee University Hospital at Gangdong Hospital	Seoul

Sponsors (8)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital	Chungbuk National University Hospital, Inha University Hospital, Inje University, Jeju National University Hospital, Korea University, Kyung Hee University Hospital at Gangdong, SMG-SNU Boramae Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	at 9 months	Yes
Secondary	All-cause death	All-cause mortality at 12 months follow-up	at 12 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	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.	Baseline	Yes
Secondary	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	Baseline	Yes
Secondary	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.	Baseline	Yes
Secondary	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.	at 12 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	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).	at 12 months	Yes
Secondary	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).	at 9 months	Yes
Secondary	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).	at 9 months	Yes
Secondary	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.	at 12 months	Yes
Secondary	Late lumen loss (in-segment)	Difference between the postprocedure and 9-month follow-up in-segment minimum lumen diameter.	at 9 months	Yes