Randomized Comparison of Abluminus DES+ Sirolimus-Eluting Stents Versus Everolimus-Eluting Stents in Coronary Artery Disease Patients With Diabetes Mellitus Global

Study Overview
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Brief Summary
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To compare in diabetic patients eligible for percutaneous coronary intervention (PCI) with minimal exclusion criteria, the efficacy and safety of Abluminus DES+ sirolimus- eluting stents (SES) versus XIENCE Everolimus-Eluting Stents (EES). At least 40% of patients are expected to be affected by multivessel coronary artery disease and 30% with acute coronary syndrome

Detailed Description
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This study aims to determine which DES will best treat the diabetic population. Specifically, the research question of this trial is to evaluate the use of a novel sirolimus-eluting stent coated with drug-eluting polymer after crimping on the balloon as compared to the standard-of-care EES in the treatment of de novo coronary artery disease in patients with diabetes mellitus. ABILITY is a prospective, multi-center, multinational, randomized, open label, 2-arm parallel group, post-approval study.

Official Title
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ABILITY Diabetes Global

Conditions
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Diabetes, Coronary Artery Disease, Acute Coronary Syndrome

Intervention / Treatment
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* Device: Abluminus DES+ Sirolimus Eluting Stent System (SES)
* Device: XIENCE Everolimus Eluting Coronary Stent System (XIENCE family)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical Inclusion Criteria Patient understands the trial requirements and the treatment procedures and provides written informed consent; Age ≥ 18 years of age (> 19 years of age for South Korea and ≥ 21 years of age for Singapore); Diabetic patient: either: Patient with a previous documented diagnosis of diabetes mellitus (Type 1 or Type 2) and currently undergoing pharmacological treatment (oral hypoglycemic agents or insulin) Newly diagnosed diabetes: either: i. Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for ≥8 hours1 or ii. Two-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) following a 75g oral glucose tolerance test or iii. HbA1c level ≥ 7% (53 mmol/mol) Patients who are newly diagnosed are included even if they are not on pharmacological treatment (oral hypoglycemic agents or insulin) Symptomatic coronary artery disease including chronic stable angina, silent ischemia, and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) Patient is eligible for percutaneous coronary intervention (PCI); Previous PCI (with balloon angioplasty or stenting) is allowed if performed >12 months before index procedure; Patient is willing and able to comply with all protocol-required follow-up evaluations. Angiographic Inclusion Criteria (visual estimate) Presence of ≥1 de novo coronary artery stenosis >50% in a native coronary artery which can be treated with a stent ranging in diameter from 2.25 to 4.0 mm and can be covered with 1 or multiple stents; and No limitation to the number of treated lesions, number of vessels, or lesion length if the patient is judged eligible for PCI by the treating physician according to the local standard of care. Exclusion Criteria: Clinical Exclusion Criteria Patient lacking capacity (i.e. patient suffering from dementia and others) to provide informed consent Patient in cardiogenic shock; Patient has known allergy to the study stent system or protocol-required concomitant medications (e.g. aspirin, clopidogrel, prasugrel, ticagrelor, heparin, stainless steel, platinum, chromium, sirolimus, everolimus, radiographic contrast material) that cannot be adequately pre-medicated; Planned surgery (cardiac and non-cardiac) within 6 months after the index procedure unless the dual-antiplatelet therapy (DAPT) can be maintained throughout the peri-surgical period; Patient undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) Patient is pregnant, nursing, or is a woman of child-bearing potential who is not surgically sterile, < 2 years postmenopausal, or does not consistently use effective methods of contraception*; Patient has any other serious medical illness (e.g., cancer, end-stage congestive heart failure) that may reduce life expectancy to less than 12 months; Acute or chronic renal dysfunction (creatinine >3.0 mg/dl); Currently participating in another investigational drug or device study. Angiographic Exclusion Criteria In-stent restenotic lesions; Lesions involving venous or arterial bypass grafts.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Target lesions should be treated in accordance with the randomization schedule after meeting the clinical and angiographic inclusion and exclusion criteria following the instruction for use of the study stent. Additional lesions (other vessels) may be staged up to 45 days post-index procedure but must be treated with the same stent. Dual antiplatelet therapy must be prescribed in alignment with the Instructions for Use of the DES and the guidelines
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Abluminus DES+ sirolimus- eluting stents (SES)<br>Enrolled patients will undergo angioplasty with Abluminus DES+ sirolimus- eluting stents (SES) and will be followed for two years. The DES procedure will be conducted in accordance with the CE mark instructions for use for the Abluminus DES+ sirolimus- eluting stents (SES). | Device: Abluminus DES+ Sirolimus Eluting Stent System (SES)<br>* The Sirolimus-eluting stent manufactured by Envision and distributed by Concept Medical<br>|
| Active Comparator: XIENCE Everolimus-Eluting Stents (EES)<br>Enrolled patients will undergo angioplasty with XIENCE Everolimus-Eluting Stents (EES) and will be followed for two years. The DES procedure will be conducted in accordance with the CE mark instructions for use for the XIENCE Everolimus-Eluting Stents (EES). | Device: XIENCE Everolimus Eluting Coronary Stent System (XIENCE family)<br>* The Everolimus-eluting stent manufactured and distributed by Abbott Vascular Santa Clara, CA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Ischemia-driven TLR | powered for non-inferiority and sequentially superiority | 1 year FU | 
| Rate of Target lesion failure TLF | composite of cardiovascular death, target vessel myocardial infarction [MI], or ischemia driven target lesion revascularization [idTLR]) | 1 year FU, powered for non-inferiority | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety composite endpoint | Safety composite endpoint of the occurrence of cardiovascular death and target-vessel myocardial infarction (MI) | 1 year (non-inferiority) | 
| co-primary TLR endpoint | In case the co-primary TLR endpoint (TLR for non-inferiority) will be demonstrated at 1 year, then the occurrence of ischemia-driven TLR at 2-year FU will be evaluated (efficacy endpoint - superiority) | 2 Year FU | 
| Composite of cardiovascular death, target vessel MI and ischemia-driven TLR (TLF) | Cardiovascular death is defined as death resulting from cardiovascular causes. The following categories may be collected: Death caused by acute MI Death caused by sudden cardiac, including unwitnessed, death Death resulting from heart failure Death caused by stroke Death caused by cardiovascular procedures Death resulting from cardiovascular hemorrhage Death resulting from other cardiovascular cause Any MI not clearly attributable to a non-target vessel will be considered as target-vessel MI. Percutaneous coronary intervention (PCI) related MI is termed type 4a MI. Coronary artery bypass grafting (CABG) related MI is termed type 5 MI. Revascularization is clinically driven if the target lesion diameter stenosis is > 50% by quantitative coronary angiography (QCA) and the subject has clinical or functional ischemia which cannot be explained by another native coronary or bypass graft lesion. | 1 year FU | 
| Bleeding | Bleeding BARC 2 or greater | 2 year |