IonMAN Trial- First in Human Study of the IoNIR Ridaforolimus-Eluting Coronary Stent System

Not Applicable

Active, not recruiting

• Conditions: Coronary Stenosis; Coronary Disease; Non-ST Elevated Myocardial Infarction; Cardiovascular Diseases
• Interventions: Device: IoNIR Ridaforolimus-Eluting Coronary Stent System

• Registration Number: NCT05364697
• Lead Sponsor: Medinol Ltd.

Brief Summary

This is a prospective, multi-center, single-arm, open-label, First in Human clinical trial to provide preliminary evidence for the safety and efficacy of the novel IoNIR stent system.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-03
• Study First Submitted QC: 2022-05-03
• Study First Posted: 2022-05-06
• Study Start: 2022-08-30
• Primary Completion: 2024-09-30
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-21
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Age ≥18 years.
2. 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).
3. Non-target vessel PCIs are allowed if performed >30 days prior to index procedure.
4. Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule.
5. 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.
6. One de novo target lesion ONLY may be treated (more than one lesion separated by less than 5 mm are considered one lesion).
7. 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 28 mm, and appropriate size IoNIR stent is 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. Relative or absolute 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, 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. More than one lesion of greater than 50% stenosis in the target vessel.
34. Complex lesions including severely calcified lesions, lesions requiring scoring/cutting and/or rotational/orbital atherectomy and/or intra-vascular lithotripsy, 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.
35. 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.
36. Ostial lesions within 3 mm of LAD, LCx, RCA ostia, lesions in the LM

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IoNIR Ridaforolimus-Eluting Coronary Stent	IoNIR Ridaforolimus-Eluting Coronary Stent System	IoNIR Ridaforolimus-Eluting Coronary Stent System

Primary Outcome Measures

Name	Time	Method
1In-stent Late Loss (LL)	1 year	In-stent Late Loss (LL) at 1 year (cohort B) assessed by quantitative coronary angiography (QCA) (Minimal Lumen Diameter (MLD) post-procedure - MLD follow-up)
Target Lesion Failure	1 year	Target Lesion Failure (composite of cardiovascular death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year

Secondary Outcome Measures

Name	Time	Method
Target vessel related MI	30 days, 6 months, 1, 2, 3, 4, 5 years	Target vessel related MI.
In-stent and in-segment Binary Restenosis	Cohort A: 30 days Cohort B: 12 months	In-stent and in-segment Binary Restenosis.
Ischemia-driven Target Vessel Revascularization	30 days, 6 months, 1, 2, 3, 4, 5 years	Ischemia-driven Target Vessel Revascularization.
OCT-determined inner layer percent neointimal hyperplasia volume	Cohort A: 30 days Cohort B: 12 months	CT-determined inner layer percent neointimal hyperplasia volume.
In-stent MLA	Cohort A: 30 days Cohort B: 12 months	In-stent Minimum Lumen Area
All-cause mortality	30 days, 6 months, 1, 2, 3, 4, 5 years	All-cause mortality.
Myocardial infarction	30 days, 6 months, 1, 2, 3, 4, 5 years	Myocardial infarction.
Target Lesion Failure	6 months, 2, 3, 4, 5 years	Target Lesion Failure (TLF)
Ischemia-driven TLR	30 days, 6 months, 1, 2, 3, 4, 5 years	Ischemia-driven Target Lesion Revascularization
Stent thrombosis	30 days, 6 months, 1, 2, 3, 4, 5 years	Stent thrombosis (ARC-2 definite and probable)
In-stent MLD	Cohort A: 30 days Cohort B: 12 months	In-stent Minimal Lumen Diameter
In-segment MLD	Cohort A: 30 days Cohort B: 12 months	In-segment (+5mm from the stent edges) MLD
Distal late loss	Cohort A: 30 days Cohort B: 12 months	Distal late loss (+5 mm from distal stent edge)
Major adverse cardiac events	30 days, 6 months, 1, 2, 3, 4, 5 years	Major adverse cardiac events (MACE; the composite rate of cardiovascular death, any MI or ischemia-driven target lesion revascularization (TLR))
Cardiovascular death	30 days, 6 months, 1, 2, 3, 4, 5 years	Cardiovascular death.
Luminal gain	Cohort A: 30 days Cohort B: 12 months	Luminal gain (MLA post-procedure - MLA pre-procedure)
NIH percentage at the MLA	Cohort A: 30 days Cohort B: 12 months	NIH (Neointimal hyperplasia) percentage at the MLA
Acute Device Success	index procedure	Acute Device Success (successful crossing and deployment with residual QCA DS \<30%).
Stent expansion	Cohort A: 30 days Cohort B: 12 months	Stent expansion.
Percentage of Covered strut	Cohort A: 30 days Cohort B: 12 months	Percentage of Covered strut (NIH thickness of \>0 μm)
Percentage of Healthy covered strut	Cohort A: 30 days Cohort B: 12 months	Percentage of Healthy covered strut (NIH thickness≥40 μm)
In-segment late loss	Cohort A: 30 days Cohort B: 12 months	In-segment (+5mm from the stent edges) late loss
Proximal late loss	Cohort A: 30 days Cohort B: 12 months	Proximal late loss (+5 mm from proximal stent edge)
In-segment minimum lumen area	Cohort A: 30 days Cohort B: 12 months	In-segment minimum lumen area (MLA)
Minimal stent area	Cohort A: 30 days Cohort B: 12 months	Minimal stent area (MSA)
Proximal late loss (+5 mm from proximal stent edge) (MLA)	Cohort A: 30 days Cohort B: 12 months	Proximal late loss (+5 mm from proximal stent edge) (MLA).
Distal late loss (+5 mm from distal stent edge) (MLA)	Cohort A: 30 days Cohort B: 12 months	Distal late loss (+5 mm from distal stent edge) (MLA).
Edge dissection	Cohort A: 30 days Cohort B: 12 months	Edge dissection.
Percentage of Area stenosis at the MLA	Cohort A: 30 days Cohort B: 12 months	Percentage of Area stenosis at the MLA.
In-stent late loss MLA	Cohort A: 30 days Cohort B: 12 months	In-stent late loss MLA.
Malapposition	Cohort A: 30 days Cohort B: 12 months	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)
Peri-strut low intensity area	Cohort A: 30 days Cohort B: 12 months	Peri-strut low intensity area (peri-strut region of homogeneous lower intensity observed without signal attenuation)
In-segment (+5 mm from the stent edges) late loss (MLA)	Cohort A: 30 days Cohort B: 12 months	In-segment (+5 mm from the stent edges) late loss (MLA).
Intraluminal mass at least 0.2 mm beyond the luminal edge of a strut	Cohort A: 30 days Cohort B: 12 months	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)
Healing score	Cohort A: 30 days Cohort B: 12 months	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); 1. Intraluminal mass (+4).; 2. Malposed and uncovered struts (+3).; 3. Uncovered struts alone (+2).; 4. Malposed struts alone (+1)

Trial Locations

Locations (4)

InCor; 🇧🇷 Sao Paulo, Brazil

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

Rabin Medical Center; 🇮🇱 Petah tikva, Israel

Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel