ABSORB II Randomized Controlled Trial

Not Applicable

Completed

Conditions: Coronary Artery Disease

Interventions: Device: Abbott Vascular ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System
Device: Abbott Vascular XIENCE Everolimus Eluting Coronary Stent System

Registration Number: NCT01425281

Lead Sponsor: Abbott Medical Devices

Brief Summary: Prospective, randomized (2:1), active control, single blinded, parallel two-arm, multi-center clinical investigation using Abbott Vascular ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System (ABSORB BVS); compared to Abbott Vascular XIENCE Everolimus Eluting Coronary Stent System (XIENCE)

Detailed Description: In the USA, ABSORB BVS is currently in development at Abbott Vascular. Not available for sale in the US.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 501

Inclusion Criteria

General Inclusion Criteria

Subject must be at least 18 years of age and less than 85 years of age.
Subject must agree not to participate in any other clinical investigation for a period of three years following the index procedure. This includes clinical trials of medication and invasive procedures. Questionnaire-based studies, or other studies that are non-invasive and do not require medication are allowed.
Subject is able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving the ABSORB BVS system and he/she or his/her legally authorized representative provides written informed consent prior to any Clinical Investigation related procedure, as approved by the appropriate Ethics Committee.
Subject must have evidence of myocardial ischemia (e.g., stable or unstable angina, silent ischemia).
Subject must be an acceptable candidate for coronary artery bypass graft (CABG) surgery
Subject must agree to undergo all clinical investigation plan-required follow-up visits, exercise testing, blood draw as well as adherence to European Society of Cardiology Guidelines and completion of quality of life questionnaires and of a subject diary to collect information including but not limited to tobacco usage, food intake, daily exercise and body weight

Angiographic Inclusion Criteria

One or two de novo native lesions each located in a different epicardial vessel.
If two treatable lesions meet the eligibility criteria, they must be in separate major epicardial vessels (left anterior descending (LAD) with septal and diagonal branches, left circumflex artery (LCX) with obtuse marginal and/or ramus intermedius branches and right coronary artery (RCA) and any of its branches).
Lesion(s) must have a visually estimated diameter stenosis of ≥50% and <100% with a TIMI flow of ≥1.
Lesion(s) must be located in a native coronary artery with Dmax by on-line quantitative coronary angiography (QCA) of ≥2.25 mm and ≤3.8 mm.
Lesion(s) must be located in a native coronary artery with lesion(s) length by on-line QCA of ≤48 mm.
Percutaneous interventions for lesions in a non-target vessel are allowed if done ≥30 days prior to or if planned to be done 2 years after the index procedure.
Percutaneous intervention for lesions in the target vessel are allowed if done >6 months prior to or if planned to be done 2 years after the index procedure.

Exclusion Criteria

Known hypersensitivity or contraindication to aspirin, both heparin and bivalirudin, antiplatelet medication specified for use in the study (clopidogrel and prasugrel and ticlopidine, inclusive), everolimus, poly (L-lactide), poly (DL-lactide), cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast sensitivity that cannot be adequately pre-medicated.
Subject has a known diagnosis of acute myocardial infarction (AMI) at any time preceding the index procedure and relevant cardiac enzymes (according to local standard hospital practice) have not returned within normal limits at the time of procedure.
Evidence of ongoing acute myocardial infarction in ECG prior to procedure
Subject has current unstable arrhythmias.
Left ventricular ejection fraction (LVEF) < 30%.
Subject has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant.
Subject is receiving or scheduled to receive chemotherapy for malignancy within 30 days prior to or after the procedure.
Subject is receiving immunosuppressant therapy and/or has known immunosuppressive or autoimmune disease (e.g. human immunodeficiency virus, systemic lupus erythematosus, rheumatoid arthritis, severe asthma requiring immunosuppressive medication, etc.).
Subject is receiving chronic anticoagulation therapy that can not be stopped and restarted according to local hospital standard procedures.
Elective surgery is planned within 2 years after the procedure that will require discontinuing either aspirin, clopidogrel, prasugrel or ticlopidine.
Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3, a white blood cell count of <3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis)
Known renal insufficiency (e.g., estimated glomerular filtration rate <60 ml/kg/1.73m² or serum creatinine level of >2.5 mg/dL, or subject on dialysis).
History of bleeding diathesis or coagulopathy or will refuse blood transfusions.
Subject has had a cerebrovascular accident (CVA) or transient ischemic neurological attack (TIA) within the past 6 months.
Pregnant or nursing subjects and those who plan pregnancy in the period up to 3 years following index procedure. (Female subjects of child-bearing potential must have a negative pregnancy test done within 28 days prior to the index procedure and contraception must be used during participation in this trial)
Other medical illness (e.g., cancer or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin etc.) as per physician judgment that may cause non-compliance with the protocol or confound the data interpretation or is associated with a limited life expectancy.
Subject is already participating in another clinical investigation that has not yet reached its primary endpoint.
Subject is belonging to a vulnerable population (per investigator's judgment, e.g., subordinate hospital staff or sponsor staff) or subject unable to read or write.

Angiographic Exclusion Criteria

Target lesion which prevents adequate (residual stenosis at target lesion(s) is ≤ 40% by visual assessment) coronary pre-dilatation.
Target lesion in left main trunk.
Aorto-ostial target lesion (within 3 mm of the aorta junction).
Target lesion located within 2 mm of the origin of the LAD or LCX.
Target lesion located distal to a diseased (vessel irregularity per angiogram and >20% stenosed lesion) arterial or saphenous vein graft.
Target lesion involving a bifurcation lesion with side branch ≥2 mm in diameter, or with a side branch <2mm in diameter requiring guide wire protection or dilatation.
Total occlusion (TIMI flow 0), prior to wire crossing
Excessive tortuosity (≥ two 45° angles), or extreme angulation (≥90 °) proximal to or within the target lesion.
Restenotic from previous intervention
Heavy calcification proximal to or within the target lesion.
Target lesion involves myocardial bridge.
Target vessel contains thrombus as indicated in the angiographic images.
Additionally clinically significant lesion(s) (≥ 40% diameter stenosis by visual assessment) for which percutaneous coronary intervention may be required <2 years after the index procedure.
Subject has received brachytherapy in any epicardial vessel (including side branches)
Subject has a high probability that a procedure other than pre-dilatation and study device implantation and (if necessary) post-dilatation will be required at the time of index procedure for treatment of the target vessel (e.g. atherectomy, cutting balloon)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABSORB BVS™	Abbott Vascular ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System	Experimental: Abbott Vascular ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System
XIENCE™	Abbott Vascular XIENCE Everolimus Eluting Coronary Stent System	Abbott Vascular XIENCE Everolimus Eluting Coronary Stent System

Primary Outcome Measures

Name	Time	Method
Absolute Difference (3 Years Post Nitrate- 3 Years Pre Nitrate) In-Scaffold Mean Lumen Diameter (MLD)	3 years	In-scaffold:Within the margins of the scaffold.
Absolute Difference (3 Years Post-nitrate - Post Procedure Post-nitrate) In-Scaffold Minimum Lumen Diameter	3 years	In-scaffold:Within the margins of the scaffold.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Target Vessel Revascularization (TVR)	5 years	Target Vessel Revascularization 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.
Number of Participants With Procedural Success	From the start of index procedure to end of index procedure	Achievement of final in-scaffold/stent residual stenosis of less than 50% by QCA with successful delivery and deployment of at least one study scaffold/stent at the intended target lesion and successful withdrawal of the delivery system for all target lesions without the occurrence of cardiac death, target vessel MI or repeat TLR during the hospital stay.
Number of Participants Experiencing All Death (Cardiac, Vascular, Non-Cardiovascular)	5 years	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in subjects with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac. * Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment. * Vascular death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause. * Non-cardiovascular death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma.
Number of Participants With Major Adverse Cardiac Events (MACE) (Cardiac Death, All MI, ID-TLR)	5 years	Major adverse cardiac events (MACE) is defined as the composite of cardiac death, all myocardial infarction, and ischemic driven target lesion revascularization (ID-TLR).
Number of Participants With All Myocardial Infarction (Per Protocol Definition)	5 years	Myocardial Infarction (MI) * Q wave MI: Development of new, pathological Q wave on the ECG. * Non-Q wave MI: Elevation of CK levels to ≥ two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves.
Number of Participants With Target Lesion Failure (TLF) (Cardiac Death, TV-MI, ID-TLR)	5 years	Target Lesion Failure is composite of Cardiac death/ Target Vessel Myocardial Infarction (TV-MI)/ Ischemic-Driven Target Lesion Revascularization (ID-TLR).
Device Success	From the start of index procedure to end of index procedure	Successful delivery and deployment of the first study scaffold/stent the intended target lesion and successful withdrawal of the delivery system with attainment of final in-scaffold/stent residual stenosis of less than 50% by quantitative coronary angiography (QCA).
Number of Participants With Target Lesion Revascularization (TLR)	5 years	Target Lesion Revascularization 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 TLR should be classified prospectively as clinically indicated \[CI\] 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 scaffold/stent.
Number of Participants With Non-Target Vessel Revascularization (Non-TVR)	5 years	Non Target Vessel Revascularization (Non-TVR) is any revascularization in a vessel other than the target vessel.
Number of Participants With Target Vessel Failure (TVF) (Cardiac Death, All MI, ID-TVR)	5 years	Target Vessel Failure (TVF) is the composite of Cardiac Death, Myocardial infarction (MI) or Ischemic-Driven Target Vessel Revascularization (ID-TVR)
Number of Participants With Non Target Vessel Revascularization (Non-TVR)	4 years	Non Target Vessel Revascularization (Non-TVR)is any revascularization in a vessel other than the target vessel.
Number of Participants With DMR (All Death, All MI, All Revascularization)	5 years	DMR is the composite of All Death, All MI, All Revascularization
Number of Participants With Subacute Stent/Scaffold Thrombosis	> 1-30 days	Scaffold/Stent thrombosis should be reported as a cumulative value at the different time points. Timings: Acute:0-24 hours;Subacute:\>24 hours-30 days;Late:30 days-1 year;Very late:\>1 year. Definite stent thrombosis occurred by either angiographic/pathologic confirmation. Angiographic confirmation:The presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent\&presence of at least 1 of the following criteria within a 48-hour time window -Acute onset of ischemic symptoms at rest;New ischemic ECG changes;Typical rise\&fall in cardiac biomarkers;Nonocclusive/Occlusive thrombus Pathological confirmation:Evidence of recent thrombus. Probable stent thrombosis may occur after intracoronary stenting due to: * Unexplained death within first 30 days * Any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis\&in the absence of any other obvious cause.
Number of Participants With All Revascularization	5 years	Revascularization: Target Lesion Revascularization (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. The target lesion is defined as the treated segment from 5 mm proximal to the scaffold and to 5 mm distal to the test scaffold. Target Vessel Revascularization (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. Non Target Lesion Revascularization (Non-TLR) is any revascularization in the target vessel for a lesion other than the target lesion. Non Target Vessel Revascularization (Non-TVR)is any revascularization in a vessel other than the target vessel.
Number of Participants Experiencing All Death/All MI	5 years	All deaths includes * Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment. * Vascular death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause. * Non-cardiovascular death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma. Myocardial Infarction (MI) * Q wave MI Development of new, pathological Q wave on the ECG. * Non-Q wave MI Elevation of CK levels to ≥ two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves.
Number of Participants With Target Lesion Failure (TLF) (Cardiac Death,(Target Vessel Myocardial Infarction(TV-MI), ID-TLR)	In-hospital (≤ 7 days of post index procedure)	Target Lesion Failure is composite of Cardiac death/ Target Vessel Myocardial Infarction (TV-MI)/ Ischemic-Driven Target Lesion Revascularization (ID-TLR).
Number of Participants With Target Lesion Failure (TLF) (Cardiac Death, Target Vessel Myocardial Infarction (TV-MI), ID-TLR)	30 days	Target Lesion Failure is composite of Cardiac death/ Target Vessel Myocardial Infarction (TV-MI)/ Ischemic-Driven Target Lesion Revascularization (ID-TLR).
Number of Participants Experiencing Cardiac Death/All MI	5 years	Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), un witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment. Myocardial Infarction (MI) Q wave MI: Development of new, pathological Q wave on the ECG. Non-Q wave MI: Elevation of CK levels to ≥ two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves.
Number of Participants With Acute Stent/Scaffold Thrombosis	<=1 day	Scaffold/Stent thrombosis should be reported as a cumulative value at the different time points. Timings: Acute:0-24 hours;Subacute:\>24 hours-30 days;Late:30 days-1 year;Very late:\>1 year. Definite stent thrombosis occurred by either angiographic/pathologic confirmation. Angiographic confirmation:The presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent\&presence of at least 1 of the following criteria within a 48-hour time window -Acute onset of ischemic symptoms at rest;New ischemic ECG changes;Typical rise\&fall in cardiac biomarkers;Nonocclusive/Occlusive thrombus Pathological confirmation:Evidence of recent thrombus. Probable stent thrombosis may occur after intracoronary stenting due to: * Unexplained death within first 30 days * Any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis\&in the absence of any other obvious cause.
Number of Participants With Acute/Subacute Stent/Scaffold Thrombosis	0-30 days	Scaffold/Stent thrombosis should be reported as a cumulative value at the different time points. Timings: Acute:0-24 hours;Subacute:\>24 hours-30 days;Late:30 days-1 year;Very late:\>1 year. Definite stent thrombosis occurred by either angiographic/pathologic confirmation. Angiographic confirmation:The presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent\&presence of at least 1 of the following criteria within a 48-hour time window -Acute onset of ischemic symptoms at rest;New ischemic ECG changes;Typical rise\&fall in cardiac biomarkers;Nonocclusive/Occlusive thrombus Pathological confirmation:Evidence of recent thrombus. Probable stent thrombosis may occur after intracoronary stenting due to: * Unexplained death within first 30 days * Any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis\&in the absence of any other obvious cause.
Number of Participants With Very Late Stent/Scaffold Thrombosis	> 365 days	Scaffold/Stent thrombosis should be reported as a cumulative value at the different time points. Timings: Acute:0-24 hours;Subacute:\>24 hours-30 days;Late:30 days-1 year;Very late:\>1 year. Definite stent thrombosis occurred by either angiographic/pathologic confirmation. Angiographic confirmation:The presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent\&presence of at least 1 of the following criteria within a 48-hour time window -Acute onset of ischemic symptoms at rest;New ischemic ECG changes;Typical rise\&fall in cardiac biomarkers;Nonocclusive/Occlusive thrombus Pathological confirmation:Evidence of recent thrombus. Probable stent thrombosis may occur after intracoronary stenting due to: * Unexplained death within first 30 days * Any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis\&in the absence of any other obvious cause.
Number of Participants With Late Stent/Scaffold Thrombosis	31-365 days	Scaffold/Stent thrombosis should be reported as a cumulative value at the different time points. Timings: Acute:0-24 hours;Subacute:\>24 hours-30 days;Late:30 days-1 year;Very late:\>1 year. Definite stent thrombosis occurred by either angiographic/pathologic confirmation. Angiographic confirmation:The presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent\&presence of at least 1 of the following criteria within a 48-hour time window -Acute onset of ischemic symptoms at rest;New ischemic ECG changes;Typical rise\&fall in cardiac biomarkers;Nonocclusive/Occlusive thrombus Pathological confirmation:Evidence of recent thrombus. Probable stent thrombosis may occur after intracoronary stenting due to: * Unexplained death within first 30 days * Any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis\&in the absence of any other obvious cause.
Number of Participants With Cumulative Stent/Scaffold Thrombosis	0-1853 days	Scaffold/Stent thrombosis should be reported as a cumulative value at the different time points. Timings: Acute:0-24 hours;Subacute:\>24 hours-30 days;Late:30 days-1 year;Very late:\>1 year. Definite stent thrombosis occurred by either angiographic/pathologic confirmation. Angiographic confirmation:The presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent\&presence of at least 1 of the following criteria within a 48-hour time window -Acute onset of ischemic symptoms at rest;New ischemic ECG changes;Typical rise\&fall in cardiac biomarkers;Nonocclusive/Occlusive thrombus Pathological confirmation:Evidence of recent thrombus. Probable stent thrombosis may occur after intracoronary stenting due to: * Unexplained death within first 30 days * Any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis\&in the absence of any other obvious cause.