This is a prospective, multi-center, non-randomized, single arm clinical trial that will be conducted at up to 40 sites in the United States and Outside United States (OUS). This study will enroll patients with symptomatic ischemic heart disease due to a single de novo lesion contained within a native coronary artery with reference vessel diameter between 2.5 mm and 4.0 mm and lesion length ≤ 24 mm that is amenable to percutaneous coronary intervention (PCI) and stent deployment. All patients will be followed at 30 days, 6 months, 9 months, 1 year and annually for 5 years post index stenting procedure.
The main objective of this study is to evaluate the safety and effectiveness of the COBRA PzF™ Coronary Stent System in the treatment of de novo lesions in native coronary arteries. The primary endpoint will be the incidence of target vessel failure (TVF, see definition below) within 270 days of treatment with the COBRA PzFTM Coronary Stent System. This rate will be compared to a performance goal derived using a meta-analysis from published historical data of the standard-of-care therapy, coronary stenting with bare metal stents. PRIMARY STUDY HYPOTHESIS The CeloNova COBRA PzFTM Study will have a primary endpoint (TVF) rate less than 19.62% and by that will meet the performance goal for bare metal stents, per the results of the historical control group combined with relevant data for EXPRESS™, Driver™, Presillion/Presillion plus™ and NIRFLEX™ stents. SECONDARY STUDY HYPOTHESIS The powered secondary endpoint for this trial is that the CeloNova COBRA PzFTM Study will have a 9-month in-stent late loss (LL) that meets or is lower than the performance goal of 1.1 mm. NUMBER OF PATIENTS 296 patients will be enrolled to account for loss to follow-up, which is estimated to be approximately 5% (resulting in 281 evaluable patients), at up to 40 sites in United States and OUS. At least 40% of subjects will be enrolled in the United States. PRIMARY ENDPOINT Target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) \[Q wave or non-Q wave, ARC-definition\], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 270 days post-procedure. SECONDARY ENDPOINTS 1. All Death at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days 2. Cardiac Death at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days 3. Major Adverse Cardiac Events (MACE), defined as cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days 4. MI at 30, 180 and 270, 360, 720, 1080, 1440, and 1800 days CeloNova Biosciences, Inc. Confidential CeloNova COBRA PzF™ Study Protocol # COBRA 2012-01 6 07 May 14 5. Clinically driven TLR at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days 6. Stroke (ischemic and hemorrhagic) at 30, 180, 270 and 360 days 7. Clinically driven TVR at 30, 180, 270 and 360 days 8. Composite Endpoint of Cardiac Death and MI at 30, 180, 270, and 360 days 9. TVF at 30, 180, and 360 days 10. Acute Success Rates 1. Device Success: Attainment of \< 30% final residual stenosis of the target lesion using only the COBRA PzFTM Coronary Stent System. 2. Lesion Success: Attainment of \< 30% final residual stenosis of the target lesion using any percutaneous method. 3. Procedure Success: Attainment of \< 30% final residual stenosis of the target lesion and no in-hospital MACE. 11. Bleeding or Vascular Complications at hospital discharge 12. Early Stent Thrombosis (ARC defined) at 30 days 13. Late Stent Thrombosis at 180, 270, and 360 days 14. Angiographic Endpoints (on first 90 evaluable patients) at 270 days (after clinical assessment) 1. In-stent late loss (Secondary Endpoint hypothesis) 2. In-segment percent diameter stenosis (%DS) (within the 5 mm margins proximal and distal to stent) 3. In-stent percent diameter stenosis (%DS) 4. In-segment late loss 5. In-segment binary restenosis (stenosis of \> 50% of the reference vessel diameter) 6. In-stent binary restenosis 7. In-stent minimum lumen diameter (MLD) 8. In-segment MLD 9. Longitudinal stent deformation 10. Stent fracture 15. Optical Coherence Tomography Endpoints (on 45 subjects) at 270 days (after clinical assessment) 1. in-stent neointimal thickness (NT) 2. Lumen area 3. Lumen volume 4. Stent area 5. Stent volume 6. Proportion of uncovered and/or malopposed struts 7. Stent fracture
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
296
Bakersfield Memorial Hospital
Bakersfield, California, United States
Mt Sinai Medical Center
Miami Beach, Florida, United States
Emory University Hospital
Atlanta, Georgia, United States
Heart Center of Indiana
Indianapolis, Indiana, United States
Louisiana Heart Hospital
Lacombe, Louisiana, United States
Target Vessel Failure (TVF)
TVF defined as cardiac death, target vessel myocardial infarction (MI \[Q wave or non-Q wave, ARC definition\], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 270 days post-procedure.
Time frame: 270 days
All Cause Mortality
Death from any cause
Time frame: 30 days
All Cause Mortality
Death from any cause
Time frame: 180 days
All Cause Mortality
Death from any cause
Time frame: 270 days
All Cause Mortality
Death from any cause
Time frame: 360 days
All Cause Mortality
Death from any cause
Time frame: 1800 days
Cardiac Mortality
Death due to any of the following: Acute myocardial infarction Cardiac perforation/pericardial tamponade Arrhythmia or conduction abnormality Cerebrovascular accident within 30 days of the procedure or cerebrovascular accident suspected of being related to the procedure Death due to complication of a cardiac procedure including bleeding, vascular repair, transfusion reaction, or bypass surgery Any death is which a cardiac cause cannot be excluded
Time frame: 30 days
Cardiac Mortality
Death due to any of the following: Acute myocardial infarction Cardiac perforation/pericardial tamponade Arrhythmia or conduction abnormality Cerebrovascular accident within 30 days of the procedure or cerebrovascular accident suspected of being related to the procedure Death due to complication of a cardiac procedure including bleeding, vascular repair, transfusion reaction, or bypass surgery Any death is which a cardiac cause cannot be excluded
Time frame: 180 days
Cardiac Mortality
Death due to any of the following: Acute myocardial infarction Cardiac perforation/pericardial tamponade Arrhythmia or conduction abnormality Cerebrovascular accident within 30 days of the procedure or cerebrovascular accident suspected of being related to the procedure Death due to complication of a cardiac procedure including bleeding, vascular repair, transfusion reaction, or bypass surgery Any death is which a cardiac cause cannot be excluded
Time frame: 270 days
Cardiac Mortality
Death due to any of the following: Acute myocardial infarction Cardiac perforation/pericardial tamponade Arrhythmia or conduction abnormality Cerebrovascular accident within 30 days of the procedure or cerebrovascular accident suspected of being related to the procedure Death due to complication of a cardiac procedure including bleeding, vascular repair, transfusion reaction, or bypass surgery Any death is which a cardiac cause cannot be excluded
Time frame: 360 days
Cardiac Mortality
Death due to any of the following: Acute myocardial infarction Cardiac perforation/pericardial tamponade Arrhythmia or conduction abnormality Cerebrovascular accident within 30 days of the procedure or cerebrovascular accident suspected of being related to the procedure Death due to complication of a cardiac procedure including bleeding, vascular repair, transfusion reaction, or bypass surgery Any death is which a cardiac cause cannot be excluded
Time frame: 1800 days
Major Adverse Cardiac Events (MACE)
Cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods
Time frame: 30 days
Major Adverse Cardiac Events (MACE)
Cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods
Time frame: 180 days
Major Adverse Cardiac Events (MACE)
Cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods
Time frame: 270 days
Major Adverse Cardiac Events (MACE)
Cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods
Time frame: 360 days
Major Adverse Cardiac Events (MACE)
Cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods
Time frame: 1800 days
Myocardial Infarction (MI-ARC Definition)
Defined as either a Q wave MI (QWMI) or Non-Q wave MI (NQMI). QWMI is defined as development of new, pathological Q waves in 2 or more contiguous leads (as assessed by the Clinical Events Committee) with post-procedure CK-MB levels elevated above normal. NQWMI is defined as any elevation of post-procedure CK-MB to \>=3 times site normal in the absence of pathological Q waves (historical definition). ARC definition includes Troponin or CK-MB \>3 x UNL
Time frame: 30 days
Myocardial Infarction (MI-ARC Definition)
Defined as either a Q wave MI (QWMI) or Non-Q wave MI (NQMI). QWMI is defined as development of new, pathological Q waves in 2 or more contiguous leads (as assessed by the Clinical Events Committee) with post-procedure CK-MB levels elevated above normal. NQWMI is defined as any elevation of post-procedure CK-MB to \>=3 times site normal in the absence of pathological Q waves
Time frame: 180 days
Myocardial Infarction (MI-ARC Definition)
Defined as either a Q wave MI (QWMI) or Non-Q wave MI (NQMI). QWMI is defined as development of new, pathological Q waves in 2 or more contiguous leads (as assessed by the Clinical Events Committee) with post-procedure CK-MB levels elevated above normal. NQWMI is defined as any elevation of post-procedure CK-MB to \>=3 times site normal in the absence of pathological Q waves
Time frame: 270 days
Myocardial Infarction (MI-ARC Definition)
Defined as either a Q wave MI (QWMI) or Non-Q wave MI (NQMI). QWMI is defined as development of new, pathological Q waves in 2 or more contiguous leads (as assessed by the Clinical Events Committee) with post-procedure CK-MB levels elevated above normal. NQWMI is defined as any elevation of post-procedure CK-MB to \>=3 times site normal in the absence of pathological Q waves
Time frame: 360 days
Myocardial Infarction (MI-ARC Definition)
Defined as either a Q wave MI (QWMI) or Non-Q wave MI (NQMI). QWMI is defined as development of new, pathological Q waves in 2 or more contiguous leads (as assessed by the Clinical Events Committee) with post-procedure CK-MB levels elevated above normal. NQWMI is defined as any elevation of post-procedure CK-MB to \>=3 times site normal in the absence of pathological Q waves
Time frame: 1800 days
Cardiac Death or MI (ARC Definition)
Composite Endpoint of Cardiac Death or MI (ARC definition)
Time frame: 30 days
Cardiac Death or MI (ARC Definition)
Composite Endpoint of Cardiac Death and MI (ARC definition)
Time frame: 180 days
Cardiac Death or MI (ARC Definition)
Composite Endpoint of Cardiac Death or MI (ARC definition)
Time frame: 270 days
Cardiac Death or MI (ARC Definition)
Composite Endpoint of Cardiac Death or MI (ARC definition)
Time frame: 360 days
Clinically Driven TLR
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 30 days
Clinically Driven TLR
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 180 days
Clinically Driven TLR
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 270 days
Clinically Driven TLR (Clinical and Angiographic Cohorts)
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 360 days
Clinically Driven TLR (Clinical Cohorts)
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 360 days
Clinically Driven TLR (Clinical and Angiographic Cohorts)
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 1800 days
Clinically Driven TLR (Clinical Cohorts)
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 1800 days
Clinically Driven TVR
Defined as a percutaneous intervention or surgical bypass of any segment of the target vessel associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis \>= 50% by QCA, or revascularization of a target vessel with diameter stenosis \>=70% by QCA without either angina or a positive functional study.
Time frame: 30 days
Clinically Driven TVR
Defined as a percutaneous intervention or surgical bypass of any segment of the target vessel associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis \>= 50% by QCA, or revascularization of a target vessel with diameter stenosis \>=70% by QCA without either angina or a positive functional study.
Time frame: 180 days
Clinically Driven TVR
Defined as a percutaneous intervention or surgical bypass of any segment of the target vessel associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis \>= 50% by QCA, or revascularization of a target vessel with diameter stenosis \>=70% by QCA without either angina or a positive functional study.
Time frame: 270 days
Clinically Driven TVR
Defined as a percutaneous intervention or surgical bypass of any segment of the target vessel associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis \>= 50% by QCA, or revascularization of a target vessel with diameter stenosis \>=70% by QCA without either angina or a positive functional study.
Time frame: 360 days
Target Vessel Failure (TVF)
TVF defined as cardiac death, target vessel myocardial infarction (MI) \[Q wave or non-Q wave, ARC definition\], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods.
Time frame: 30 days
Target Vessel Failure (TVF)
TVF defined as cardiac death, target vessel myocardial infarction (MI) \[Q wave or non-Q wave, ARC definition\], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods.
Time frame: 180 days
Target Vessel Failure (TVF)
TVF defined as cardiac death, target vessel myocardial infarction (MI) \[Q wave or non-Q wave, ARC definition\], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods.
Time frame: 360 days
Stroke (Ischemic and Hemorrhagic)
Defined as sudden onset of vertigo, numbness, dysphasia, weakness, visual field defects, dysarthria or other focal neurological deficits due to vascular lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that persists more than 24 hours.
Time frame: 30 days
Stroke (Ischemic and Hemorrhagic)
Defined as sudden onset of vertigo, numbness, dysphasia, weakness, visual field defects, dysarthria or other focal neurological deficits due to vascular lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that persists more than 24 hours.
Time frame: 180 days
Stroke (Ischemic and Hemorrhagic)
Defined as sudden onset of vertigo, numbness, dysphasia, weakness, visual field defects, dysarthria or other focal neurological deficits due to vascular lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that persists more than 24 hours.
Time frame: 270 days
Device Success
Attainment of \<30% final residual stenosis of the target lesion using only the COBRA PzF Coronary Stent System
Time frame: 30 days
Stroke (Ischemic and Hemorrhagic)
Defined as sudden onset of vertigo, numbness, dysphasia, weakness, visual field defects, dysarthria or other focal neurological deficits due to vascular lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that persists more than 24 hours.
Time frame: 360 days
Lesion Success
Attainment of \<30% final residual stenosis of the target lesion using any percutaneous method
Time frame: 30 days
Procedure Success
Attainment of \<30% final residual stenosis of the target lesion and no in-hospital MACE
Time frame: 30 days
Bleeding or Vascular Complications
Bleeding Complications: Procedure-related hemorrhagic event that requires a transfusion and/or surgical intervention Vascular Complications: May include pseudo aneurysm, arteriovenous fistula (AVF), peripheral ischemia/nerve injury, and vascular event requiring transfusion or surgical repair
Time frame: 30 days
Early Stent Thrombosis (ARC Definition)
Early Stent Thrombosis (ARC Definition) 0-30 days post index procedure
Time frame: 30 days
Late Stent Thrombosis
Stent Thrombosis after 30 days and on or before 180 days
Time frame: 180 days
Late Stent Thrombosis
Stent Thrombosis after 30 days and on or before 270 days
Time frame: 270 days
Late Stent Thrombosis
Stent Thrombosis after 30 days and on or before 360 days
Time frame: 360 days
Definite and Probable Stent Thrombosis
Defined as a percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion associated with positive functional ischemia study or ischemic symptoms AND an angiographic minimal lumen diameter stenosis of \>= 50% by QCA, or revascularization of a target vessel with a diameter stenosis of \>=70% by QCA without either angina or a positive functional study.
Time frame: 1800 days
In-Segment Percent Diameter Stenosis
Relative changes that occur in the percent diameter stenosis of the segment and are provided by the following relationship: % diameter stenosis= (1-\[MLD/Reference diameter\]) x 100
Time frame: 270 days
In-Stent and In-Segment MLD and Late Loss
* In-stent and in-Segment minimal lumen diameter obtained immediately after stent implantation and at angiographic assessment at 270 days. * In-stent or in-segment late loss was defined as the difference between minimum lumen diameter (in-stent or in-segment) immediately after implantation and that obtained at angiographic follow-up at 270 days.
Time frame: 270 days
Angiographic Endpoints
Angiographic subset included 115 of the 296 enrolled. Therefore, the overall number of participants analyzed for this outcome measure is 115.
Time frame: 270 days
In-stent Neointimal Thickness (INT)
in-stent neointimal thickness assessed by Optical Coherence Tomography
Time frame: 270 days
Percentage of Uncovered and/or Malapposed Struts
This measure assess the average proportion of uncovered and or malapposed struts measured by Optical Coherence Tomography in participants
Time frame: 270 days
Lumen and Stent Area Measurements
Optical Coherence Tomography assessment of the lumen and stent area after the clinical follow up at 270 days
Time frame: 270 days
Lumen and Stent Volume
Optical Coherence Tomography assessment of the lumen and stent volume after the clinical follow up at 270 days
Time frame: 270 days
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