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

Cardiovascular Diseases Clinical Trial

— IonMAN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05364697
• Other study ID #: IoNIR-001
• Status: Recruiting
• Phase: N/A
• Start date: August 30, 2022
• Est. completion date: December 2028

Study information

• Verified date: March 2023
• Source: Medinol Ltd.
• Contact: Brenda Koltun Reuven
• Phone: 972-3-767-9000
• Email: brendak[@]medinol.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2028
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Disease
• Coronary Stenosis
• Infarction
• Myocardial Infarction
• Non-ST Elevated Myocardial Infarction

Intervention

Device:
• IoNIR Ridaforolimus-Eluting Coronary Stent System
The IoNIR Ridaforolimus-Eluting Coronary Stent System is a sterile single-use device/drug combination product, comprised of a cobalt chromium (CoCr) alloy-based stent coated with a bioresorbable polymer mesh which is embedded with drug, mounted on a Rapid Exchange (RX) delivery system.

Locations

Country	Name	City	State
Brazil	InCor	Sao Paulo
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah tikva
Israel	Sourasky Medical Center	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Medinol Ltd.

Countries where clinical trial is conducted

Brazil,  Israel, 

Outcome

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