Clinical trial NCT01826552: Comparison of the Angiographic Result of the Orsiro Hybrid Stent With Resolute Integrity Stent
Official title: Multicenter, Randomized, Open Label, Parallel Group Study to Evaluate the Safety and Efficacy of Orsiro Hybrid Drug Eluting Stent
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: 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
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Jeju National University Hospital
name: Chungbuk National University Hospital
name: SMG-SNU Boramae Medical Center
name: Korea University
name: Inje University
name: Kyung Hee University Hospital at Gangdong
name: Inha University Hospital
First posted: 2013-04-08
Enrollment: 372
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Late lumen loss (in-stent)
timeFrame: at 9 months
Secondary outcomes:
measure: All-cause death
timeFrame: at 12 months
measure: Cardiac death
timeFrame: at 12 months
measure: Target lesion revascularization
timeFrame: at 12 months
measure: Target vessel revascularization
timeFrame: at 12 months
measure: Target-vessel related myocardial infarction
timeFrame: at 12 months
measure: Non-target vessel related myocardial infarction
timeFrame: at 12 months
measure: Clinical device success
timeFrame: Baseline
measure: Clinical lesion success
timeFrame: Baseline
measure: Clinical procedure success
timeFrame: Baseline
measure: Stent thrombosis
timeFrame: at 12 months
measure: Target lesion failure
timeFrame: at 12 months
measure: Patient-oriented composite outcome
timeFrame: at 12 months
measure: In-stent/in-segment % diameter stenosis
timeFrame: at 9 months
measure: In-stent/in-segment binary restenosis
timeFrame: at 9 months
measure: Clinically driven revascularization
timeFrame: at 12 months
measure: Late lumen loss (in-segment)
timeFrame: at 9 months
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk University Hospital
city: Ilsan
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Jeju
country: Korea, Republic of
facility: Jeju University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong Hospital
Study officials:
affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Seoul National University and Cardiovascular Center, Seoul National University Bundang Hospital
name: Tae-Jin Youn, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Seoul National University Bundang Hospital
name: Dong-Ju Choi, MD,PhD
role: STUDY_CHAIR
affiliation: Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Seoul National University Bundang Hospital
name: In-Ho Chae, MD,PhD
role: STUDY_DIRECTOR
References:
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.