IonMAN II Trial- Early Feasibility Study of the IoNIR Ridaforolimus-Eluting Coronary Stent System

Study Overview
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Brief Summary
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This is a prospective, multi-center, single-arm, open-label, early feasibility study to provide preliminary evidence for the safety and efficacy of the novel IoNIR stent system

Official Title
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IonMAN II Trial- Early Feasibility Study of the IoNIR Ridaforolimus-Eluting Coronary Stent System

Conditions
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Coronary Stenosis, Coronary Artery Disease

Intervention / Treatment
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* Device: IoNIR Ridaforolimus-Eluting Coronary Stent System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Patient with an indication for PCI including NSTEMI (biomarkers have peaked or are falling), angina (stable or unstable), silent ischemia (in absence of symptoms a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or FFR ≤0.80, Pd/Pa≤0.91or iFR, RFR, DFR, DPR≤0.89 must be present). Non-target vessel PCIs are allowed if performed >30 days prior to index procedure. Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule. Staged procedures are allowed as long as the IoNIR stent is implanted in the last procedure and at least 30 days have elapsed between the previous procedure and the IoNIR PCI. A maximum of two vessels and up to two lesions may be treated (two lesions separated by up to 10mm that can be covered by a single stent are considered as one lesion). Lesions requiring scoring/cutting and/or rotational/orbital atherectomy and/or intra-vascular lithotripsy are allowed. Overlapping stents are allowed. Target lesion must be in a major native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.0 mm and lesion length of up to 40 mm, and appropriate size IoNIR stents are available. Exclusion Criteria: 1. ST Segment Elevation MI within past 30 days. 2. NSTEMI with biomarkers that have not peaked. 3. Significant valvular disease or planned valvular intervention. 4. PCI within the 30 days preceding the baseline procedure. 5. PCI in the target vessel within 12 months of the baseline procedure. 6. Planned staged procedures (coronary or valvular), where the study stent is implanted in the first stage. 7. Brachytherapy in conjunction with the baseline procedure. 8. Known history of stent thrombosis. 9. Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP. 10. Subject is intubated. 11. Known LVEF <30%. 12. Contraindication to DAPT for 6 months in non-ACS patients and 12 months in ACS patients (including planned surgeries that cannot be delayed). 13. Subject has an indication such as atrial fibrillation for oral anticoagulation/prolonged heparinization (i.e., use of coumadin/DOAC (NOAC) or prolonged enoxaparin/heparin therapy is not allowed). 14. eGFR <60 mL/min. 15. Hemoglobin <10 g/dL. 16. Platelet count <100,000 cells/mm3 or >700,000 cells/mm3. 17. White blood cell (WBC) count <3,000 cells/mm3. 18. Clinically significant liver disease. 19. Active peptic ulcer or active bleeding from any site. 20. Bleeding from any site within the previous 8 weeks requiring active medical or surgical attention. 21. If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath. 22. History of bleeding diathesis or coagulopathy and patients that refuse blood transfusions. 23. Cerebrovascular accident or transient ischemic attack within the past 6 months, or any permanent neurologic defect attributed to CVA. 24. Known allergy to the study stent components (cobalt, nickel, chromium, molybdenum, platinum, PDLG, PLC, or limus drugs (ridaforolimus, zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs or any other analogue or derivative or similar compounds). 25. Known allergy to protocol-required concomitant medications such as aspirin, or P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), heparin and bivalirudin, or iodinated contrast allergy that cannot be adequately pre-medicated. 26. Any co-morbid condition that may cause non-compliance with the protocol (e.g., dementia, substance abuse, etc.) or reduced life expectancy to <24 months (e.g., cancer, severe heart failure, severe lung disease). 27. Patient is participating in or plans to participate in any other investigational drug or device clinical trial that has not reached its primary endpoint. 28. Women who are pregnant or breastfeeding. 29. Women who intend to become pregnant within 12 months after the baseline procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the baseline procedure). 30. Patient has received an organ transplant or is on a waiting list for an organ transplant. 31. Patient is receiving or scheduled to receive chemotherapy within 30 days before or any time after the baseline procedure. 32. Patient is receiving oral or intravenous immunosuppressive therapy or has known life-limiting immunosuppressive or autoimmune disease (e.g., HIV). Corticosteroids are allowed. 33. Complex lesions including severely calcified lesions, presence of visible thrombus, chronic total occlusions, bifurcation lesions (side branch diameter ≥2.0 mm), tortuous lesions, restenotic lesions, left main lesions, ectasia, aneurysm and any bypass graft lesions. 34. Another lesion in a target or non-target vessel (including all side branches) is present that requires or has a high probability of requiring PCI within 12 months after the baseline procedure. 35. Ostial lesions within 3 mm of origin of LAD, LCx, lesions in the LM.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IoNIR Ridaforolimus-Eluting Coronary Stent<br>IoNIR Ridaforolimus-Eluting Coronary Stent System | Device: IoNIR Ridaforolimus-Eluting Coronary Stent System<br>* The IoNIR Ridaforolimus-Eluting Coronary Stent System is a sterile single-use device/drug combination product, comprised of a cobalt chromium (CoCr) alloybased stent coated with a bioresorbable polymer mesh which is embedded with drug, mounted on a Rapid Exchange (RX) delivery system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-stent Late Loss (LL) | In-stent Late Loss (LL) at 13 months assessed by quantitative coronary angiography (QCA) (Minimal Lumen Diameter (MLD) post-procedure - MLD follow-up (US patients only)) | 13 months | 
| Target Lesion Failure | Target Lesion Failure (composite of cardiovascular death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac events | Major adverse cardiac events (MACE; the composite rate of cardiovascular death, any MI or ischemia-driven target lesion revascularization (TLR)). | 30 days, 6 months, 1,2,3,4,5 years | 
| All-cause mortality | All-cause mortality | 30 days, 6 months, 1,2,3,4,5 years | 
| Cardiovascular death | Cardiovascular death | 30 days, 6 months, 1,2,3,4,5 years | 
| Myocardial infarction | Myocardial infarction | 30 days, 6 months, 1,2,3,4,5 years | 
| Target vessel related MI | Target vessel related MI | 30 days, 6 months, 1,2,3,4,5 years | 
| Target Lesion Failure | Target Lesion Failure | 6 months, 2, 3, 4, 5 years | 
| Ischemia-driven TLR | Ischemia-driven TLR | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Ischemia-driven Target Vessel Revascularization | Ischemia-driven Target Vessel Revascularization | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Stent thrombosis | Stent thrombosis (ARC-2 definite and probable). | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Acute Device Success | Acute Device Success (successful crossing and deployment with residual QCA DS <30%) | index procedure | 
| Luminal gain | Luminal gain (MLD post-procedure - MLD pre-procedure) | 13 months - US patients only | 
| In-stent MLD | In-stent MLD | 13 months - US patients only | 
| In-segment MLD | In-segment (+5mm from the stent edges) MLD | 13 months - US patients only | 
| In-segment late loss | In-segment (+5mm from the stent edges) late loss | 13 months - US patients only | 
| Proximal late loss | Proximal late loss (+5 mm from proximal stent edge) | 13 months - US patients only | 
| Distal late loss | Distal late loss (+5 mm from proximal stent edge) | 13 months - US patients only | 
| In-stent and in-segment Binary Restenosis | In-stent and in-segment Binary Restenosis | 13 months - US patients only | 
| OCT-determined inner layer percent neointimal hyperplasia volume | OCT-determined inner layer percent neointimal hyperplasia volume | 13 months - US patients only | 
| In-stent MLA | In-stent MLA | 13 months - US patients only | 
| In-segment minimum lumen area (MLA) | In-segment minimum lumen area (MLA) | 13 months - US patients only | 
| Minimal stent area (MSA) | Minimal stent area (MSA) | 13 months - US patients only | 
| Stent expansion | Stent expansion | 13 months - US patients only | 
| Edge dissection | Edge dissection | 13 months - US patients only | 
| % NIH at the MLA | % NIH at the MLA | 13 months - US patients only | 
| % Area stenosis at the MLA | % Area stenosis at the MLA | 13 months - US patients only | 
| Luminal gain (MLA post-procedure - MLA pre-procedure) | Luminal gain (MLA post-procedure - MLA pre-procedure) | 13 months - US patients only | 
| In-stent late loss MLA | In-stent late loss MLA | 13 months - US patients only | 
| In-segment (+5 mm from the stent edges) late loss (MLA). | In-segment (+5 mm from the stent edges) late loss (MLA). | 13 months - US patients only | 
| Proximal late loss (+5 mm from proximal stent edge) (MLA) | Proximal late loss (+5 mm from proximal stent edge) (MLA) | 13 months - US patients only | 
| Distal late loss (+5 mm from distal stent edge) (MLA) | Distal late loss (+5 mm from distal stent edge) (MLA) | 13 months - US patients only | 
| Intraluminal mass at least 0.2 mm beyond the luminal edge of a strut | Intraluminal mass at least 0.2 mm beyond the luminal edge of a strut (Intraluminal mass attached to the vessel is defined as an irregularly shaped structure in contact with the luminal contour, a free intraluminal mass is defined as an isolated structure in the lumen without contact to the vessel wall) | 13 months - US patients only | 
| Malapposition | Malapposition (stent struts clearly separated from the vessel wall (lumen border/plaque surface) without tissue behind the struts with a distance from the adjacent intima of ≥0.2 mm not associated with any side branch) | 13 months - US patients only | 
| % Covered strut | % Covered strut (NIH thickness of >0 μm). | 13 months - US patients only | 
| % Healthy covered strut | % Healthy covered strut (NIH thickness≥40 μm). | 13 months - US patients only | 
| Peri-strut low intensity area | Peri-strut low intensity area (peri-strut region of homogeneous lower intensity observed without signal attenuation). | 13 months - US patients only | 
| Healing score | Healing score (defined as % intraluminal mass [=intraluminal mass volume/stent volume] ×4 + % malposed and uncovered struts ×3 + (% uncovered struts alone ×2 + % malposed struts alone ×1) at 13 months. Intraluminal mass (+4). Malposed and uncovered struts (+3). Uncovered struts alone (+2). Malposed struts alone (+1). | 13 months - US patients only |