Efficacy of Everolimus-Eluting Versus Zotarolimus-Eluting Sten for Coronary Lesions in Acute Myocardial Infarction (EVERZOTA)
Primary Purpose
Myocardial Infarction
Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Everolimus eluting stent
Zotarolimus eluting stent
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Infarction focused on measuring drug-eluting stent, everolimus, zotarolimus, myocardial ischemia, cardiovascular diseases, MACE, safety
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years
- Chest pain duration more than 10 minutes
- At least on of the following criteria
- A. ECG change (T inversion, ST depression or ST elevation)
- B. Cardiac enzyme elevation more than upper normal limit
- Significant coronary artery stenosis (>50% by visual estimate)
- The patient or guardian agrees to the study
Exclusion Criteria:
- Stent thrombosis
- Left main disease
- Cardiogenic shock
- Cronic kidney disease or renal failure requiring hemodialysis
- History of bleeding diathesis or known coagulopathy
- Gastrointestinal or genitourinary bleeding within the prior 3 months
- History of major surgery within 2 months
- Planned surgery requiring cessation of clopidogrel within 12 months of percutaneous coronary intervention (PCI)
- Serious patients whose life expectancy <1 year or severe infectious status
Sites / Locations
- Yonsei University Wonju College of Medicine; Wonju Severance Christian Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Xience V stent group
Endeavor resolute group
Arm Description
Xience V (Everolimus eluting stent) insertion in patients with acute myocardial infarction
Endeavor resolute (Zotarolimus eluting stent) insertion in patients with acute myocardial infarction
Outcomes
Primary Outcome Measures
Device-oriented Composite Outcome
defined as a composite of cardiac death, Myocardial infarction not clearly attributable to a nontarget vessel and target lesion revascularization
Secondary Outcome Measures
Device-oriented Composite Outcome
defined as a composite of all-cause mortality, any MI (includes non-target vessel territory) and repeat revascularization (includes all target and non-target vessel)
Stent Thrombosis
Definite and probable stent thrombosis
Any Bleeding
Full Information
NCT ID
NCT01347554
First Posted
April 27, 2011
Last Updated
September 23, 2014
Sponsor
Yonsei University
Collaborators
Medtronic
1. Study Identification
Unique Protocol Identification Number
NCT01347554
Brief Title
Efficacy of Everolimus-Eluting Versus Zotarolimus-Eluting Sten for Coronary Lesions in Acute Myocardial Infarction
Acronym
EVERZOTA
Official Title
Comparison of the Efficacy of Everolimus-Eluting Versus Zotarolimus-Eluting Stent for Coronary Lesions in Acute Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University
Collaborators
Medtronic
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Most of the previous data regarding the efficacy of the everolimus-eluting stent (EES) was derived from studies comparing EES with bare metal stent (BMS) or EES with paclitaxel-eluting (PES). Although sirolimus-eluting stents (SES) have been shown to be the most efficacious drug regarding inhibition of neointima and late loss, there have been no previous head to head comparisons between EES and zotarolimus-eluting stent (ZES). Both everolimus and sirolimus are macrocyclic lactones that target the mTOR (mammalian target of rapamycin) to reduce vascular smooth muscle proliferation after vessel injury and therefore in principle may show similar results after stenting in humans. Data pooled from the EES arm that received follow up angiography in the SPIRIT III trial and the SES arm in the SIRIUS trial show similar rates of binary restenosis and late loss. However, the stent and polymer platform is not the same between the EES and ZES and it is reported that the EES system has the thinnest stent + polymer thickness (88.6um) of all of the previously KFDA-approved drug-eluting stent (DES). In addition, there are no data available on the efficacy of the EES and ZES in "real world" lesions other than the selected lesions studied in the previous trials, such as acute myocardial infarction.
Detailed Description
Previous randomized trials have shown the efficacy of a slow-release polymeric sirolimus-eluting stent (CYPHER, Cordis, Warren, NJ, USA), paclitaxel-eluting stent (TAXUS, Boston Scientific, Natick, MA, USA), and zotarolimus-eluting stent (Endeavor, Medtronic, Minneapolis, MN, USA) over bare metal stents in reducing neointimal hyperplasia, late luminal loss, and angiographic restenosis leading to decreased target lesion revascularization. The everolimus-eluting stent (XIENCE V, Abott Vascular, Santa Clara, CA, USA, PROMUS, Boston Scientific, Natick, MA, USA) is a newly developed drug eluting stent using the MULTILINK VISION® stent platform combined with the drug everolimus contained in a polymer coating.
In the first-in-man SPIRIT First clinical trial, XIENCE V showed a significant benefit over the bare metal VISION stent. Compared with late loss of 0.85 ± 0.36mm in the VISION arm, XIENCE V reduced late loss by 88% (0.10 ± 0.23mm). Also the clinical safety of XIENCE V was confirmed with a 6-month MACE rate of 7.7%. In the SPIRIT II clinical trial, which compared the efficacy and safety of the XIENCE V stent versus the TAXUS PECSS stent, the primary endpoint was met showing a non-inferiority of the XIENCE V compared with the TAXUS regarding in-stent late loss at 180 days. Actually, XIENCE V was superior to TAXUS and reduced in-stent late loss by 72% from a mean of 0.36 mm to 0.11 mm. In addition, analysis of other key clinical endpoints showed a lower rate of ischemia driven MACE (2.7% vs. 6.5% for XIENCE V vs. TAXUS) and protocol-defined stent thrombosis (0.5% vs. 1.3% for XIENCE V vs. TAXUS). The lower rate of ischemia driven MACE at 180 days was sustained through 1 year and there were no new instances of late stent thrombosis in either group up to 1 year.
The SPIRIT III RCT was a prospective, 2:1 randomized, active-controlled, single blinded, parallel, multi-center clinical evaluation of the XIENCE V Everolimus Eluting Coronary Stent System (XIENCE V EECSS) compared to TAXUS Paclitaxel Eluting Coronary Stent System (TAXUS PECSS) in the treatment of up to two de novo lesions. This pivotal clinical trial was designed to demonstrate the non-inferiority of the XIENCE V EECSS to the TAXUS PECSS. Patients were randomized 2:1 to XIENCE V or TAXUS and the primary endpoint was in-segment late loss at 240 days. The results showed a mean in-segment late loss of 0.14mm for XIENCE V and 0.28 mm for TAXUS (p<0.001 for non-inferiority, p=0.0037 for superiority). The secondary endpoint, which was ischemia-driven target vessel failure (TVF), was 7.6% for XIENCE V and 9.7% for TAXUS, confirming the non-inferiority of XIENCE V. Furthermore, the rate of definite and probable stent thrombosis was 1.1% and 0.6% for XIENCE V and TAXUS, respectively.
With a recent approval of new DES, zotarolimus-eluting stent (Endeavor, Medtronic, Minneapolis, MN), other comparison studies have been conducted to compare Endeavor zotarolimus-eluting stent with the sirolimus-eluting stent and paclitaxel-eluting stent. zotarolimus and sirolimus share some common structural and biological properties. In vitro data suggest that sirolimus and tetrazole containing rapamycin analogs have similar inhibitory effects in a mixed lymphocyte reaction assay. The ENDEAVOR clinical trials are currently in progress to evaluate a phosphoryl choline (PC)-coated zotarolimus-eluting stent(ZES) for the prevention of restenosis. The Endeavor zotarolimus-eluting stent utilizes a cobalt alloy balloon-expandable stent (Driver; Medtronic) with a geometry similar to the stainless steel stent used in this preliminary study (S7; Medtronic). The Endeavor ZES also employees a PC strut surface coating as the drug delivery reservoir with a dose of 10 g/mm of ABT-578. The Endeavor (ZES), however, differs from the stent used in this experimental study by the addition of a drug-free PC topcoat to serve as a diffusion barrier to retard drug release from the polymer reservoir. Angiographic analysis at 4 months in the 100-patient focal de novo lesion ENDEAVOR I feasibility study demonstrated a mean in-stent percent diameter stenosis of approximately 14% and a late lumen loss of 0.3 mm with a low frequency of target lesion revascularization (1%). The clinical outcomes from the ENDEAVOR II (1,500 patients randomized to ABT-578 or bare metal stent) and the ENDEAVOR III (436 patients randomized 3:1 to ABT-578 or Cypher) trials as well as other ongoing studies showed efficacy of the PC-coated ABT-578-eluting stent. In ENDEAVOR III study, the Endeavor stent had larger late loss and higher binary restenosis in both the analysis segment and stented segment.
Most of the previous data regarding the efficacy of the EES was derived from studies comparing EES with BMS or EES with PES. Although sirolimus eluting stents (SES) have been shown to be the most efficacious drug eluting stent regarding inhibition of neointima and late loss, there have been no previous head to head comparisons between EES and ZES. Both everolimus and sirolimus are macrocyclic lactones that target the mTOR (mammalian target of rapamycin) to reduce vascular smooth muscle proliferation after vessel injury and therefore in principle may show similar results after stenting in humans. Data pooled from the EES arm that received follow up angiography in the SPIRIT III trial and the SES arm in the SIRIUS trial show similar rates of binary restenosis and late loss. However, the stent and polymer platform is not the same between the EES and ZES and it is reported that the EES system has the thinnest stent + polymer thickness (88.6um) of all of the previously KFDA-approved DES. In addition, there are no data available on the efficacy of the EES and ZES in "real world" lesions other than the selected lesions studied in the previous trials, such as acute myocardial infarction.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
Keywords
drug-eluting stent, everolimus, zotarolimus, myocardial ischemia, cardiovascular diseases, MACE, safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
461 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Xience V stent group
Arm Type
Active Comparator
Arm Description
Xience V (Everolimus eluting stent) insertion in patients with acute myocardial infarction
Arm Title
Endeavor resolute group
Arm Type
Active Comparator
Arm Description
Endeavor resolute (Zotarolimus eluting stent) insertion in patients with acute myocardial infarction
Intervention Type
Device
Intervention Name(s)
Everolimus eluting stent
Other Intervention Name(s)
Xience V, Promus or Promus element
Intervention Description
Comparison of the safety and efficacy between everolimus-eluting stent and zotarolimus-eluting stent resolute
Intervention Type
Device
Intervention Name(s)
Zotarolimus eluting stent
Other Intervention Name(s)
Endeavor resolute
Intervention Description
Comparison of the safety and efficacy between everolimus-eluting stent and zotarolimus-eluting stent resolute
Primary Outcome Measure Information:
Title
Device-oriented Composite Outcome
Description
defined as a composite of cardiac death, Myocardial infarction not clearly attributable to a nontarget vessel and target lesion revascularization
Time Frame
Two year
Secondary Outcome Measure Information:
Title
Device-oriented Composite Outcome
Description
defined as a composite of all-cause mortality, any MI (includes non-target vessel territory) and repeat revascularization (includes all target and non-target vessel)
Time Frame
Two years
Title
Stent Thrombosis
Description
Definite and probable stent thrombosis
Time Frame
Two years
Title
Any Bleeding
Time Frame
Two year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 18 years
Chest pain duration more than 10 minutes
At least on of the following criteria
A. ECG change (T inversion, ST depression or ST elevation)
B. Cardiac enzyme elevation more than upper normal limit
Significant coronary artery stenosis (>50% by visual estimate)
The patient or guardian agrees to the study
Exclusion Criteria:
Stent thrombosis
Left main disease
Cardiogenic shock
Cronic kidney disease or renal failure requiring hemodialysis
History of bleeding diathesis or known coagulopathy
Gastrointestinal or genitourinary bleeding within the prior 3 months
History of major surgery within 2 months
Planned surgery requiring cessation of clopidogrel within 12 months of percutaneous coronary intervention (PCI)
Serious patients whose life expectancy <1 year or severe infectious status
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seung-Hwan Lee, MD, PhD
Organizational Affiliation
Division of Cardiology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yonsei University Wonju College of Medicine; Wonju Severance Christian Hospital
City
Wonju
ZIP/Postal Code
220-701
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
25503419
Citation
Ahn SG, Choi HH, Lee JH, Lee JW, Youn YJ, Yoo SY, Cho BR, Lee SH, Yoon J. The impact of initial and residual thrombus burden on the no-reflow phenomenon in patients with ST-segment elevation myocardial infarction. Coron Artery Dis. 2015 May;26(3):245-53. doi: 10.1097/MCA.0000000000000197.
Results Reference
derived
Learn more about this trial
Efficacy of Everolimus-Eluting Versus Zotarolimus-Eluting Sten for Coronary Lesions in Acute Myocardial Infarction
We'll reach out to this number within 24 hrs