Clinical trial NCT02834806: BIONICS Israel Trial
Official title: BioNIR Ridaforolimus Eluting Coronary Stent System (BioNIR) In Coronary Stenosis Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stenosis
Lead sponsor: Medinol Ltd.
Sponsor class: INDUSTRY
First posted: 2016-07-15
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to assess the device success and the safety of Medinol's Drug Eluting Stent - BioNIR - with a modified delivery system. The BioNIR Ridaforolimus Eluting Coronary Stent System is a single use device/drug combination product comprising:

* A mounted Cobalt Chromium (CoCr) alloy based stent
* A Rapid Exchange (RX) delivery system
* A polymer matrix coating - Poly n-butyl methacrylate (PBMA) and CarboSil®
* Ridaforolimus drug - CAS Registry Number: 572924-54-0 It is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to lesions in vessels with reference diameters of 2.5 mm to 4.25 mm, including complex lesions.

Detailed description: This is a prospective, multi-center, single arm, open label, clinical trial. Lesions planned to be treated must be declared and recorded at time of enrollment. Planned staged procedures, if necessary, must be declared immediately post procedure. Clinical follow-up will be performed at 30 days.

Telephone follow-ups will be performed at 6 months and 1 year post procedure.

Eligibility criteria: Inclusion Criteria:

1. Patient with an indication for PCI including 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 must be present), NSTEMI, or recent STEMI. For STEMI the time of presentation to the first treating hospital, whether a transfer facility or the study hospital, must be \>24 hours prior to enrollment and enzyme levels (CK-MB or Troponin) demonstrating that either or both enzyme levels have peaked.
2. Non-target vessel PCI are allowed prior to enrollment depending on the time interval and conditions as follows:

   During Baseline Procedure:

   PCI of non-target vessels performed during the baseline procedure itself immediately prior to enrollment if successful and uncomplicated defined as: \<50% visually estimated residual diameter stenosis, TIMI Grade 3 flow, no dissection ≥ NHLBI type C, no perforation, no persistent ST segment changes, no prolonged chest pain, no TIMI major or BARC type 3 bleeding.

   Less than 24 hours prior to Baseline Procedure:

   Not allowed (see exclusion criteria #2). 24 hours-30 days prior to Baseline Procedure: PCI of non-target vessels 24 hours to 30 days prior to enrollment if successful and uncomplicated as defined above.

   In addition, in cases where non-target lesion PCI has occurred 24-72 hours prior to the baseline procedure, at least 2 sets of cardiac biomarkers must be drawn at least 6 and 12 hours after the non-target vessel PCI.

   If cardiac biomarkers are initially elevated above the local laboratory upper limit of normal, serial measurements must demonstrate that the biomarkers are falling.

   Over 30 days prior to Baseline Procedure:

   a. PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated.
3. Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule.

   Angiographic inclusion criteria (visual estimate):
4. Target lesion(s) must be located in a native coronary artery or bypass graft conduit with visually estimated diameter of ≥2.5 mm to ≤4.25 mm.
5. Complex lesions are allowed including calcified lesions (lesion preparation with scoring/cutting and rotational atherectomy are allowed), presence of thrombus, CTO, bifurcation lesions (except as noted in exclusion criteria #30), ostial RCA lesions, tortuous lesions, bare metal stent restenotic lesions, protected left main lesions, and saphenous vein graft lesions.
6. Overlapping stents are allowed.

Exclusion Criteria:

General Exclusion Criteria:

1. STEMI within 24 hours of initial time of presentation to the first treating hospital, whether at a transfer facility or the study hospital or in whom enzyme levels (either CK-MB or Troponin) have not peaked.
2. PCI within the 24 hours preceding the baseline procedure.
3. Non-target lesion PCI in the target vessel within 12 months of the baseline procedure.
4. History of stent thrombosis.
5. 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.
6. Subject is intubated.
7. Known LVEF \<30%.
8. 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, or subject is indicated for chronic oral anticoagulant treatment).
9. Calculated creatinine clearance \<30 mL/min using Cockcroft-Gault equation (\<40 mL/min for subjects participating in the angiographic follow-up sub-study).
10. Hemoglobin \<10 g/dL.
11. Platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3.
12. White blood cell (WBC) count \<3,000 cells/mm3.
13. Clinically significant liver disease.
14. Active peptic ulcer or active bleeding from any site.
15. Bleeding from any site within the prior 8 weeks requiring active medical or surgical attention.
16. If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath.
17. History of bleeding diathesis or coagulopathy or will refuse blood transfusions.
18. Cerebrovascular accident or transient ischemic attack within the past 6 months, or any permanent neurologic defect attributed to CVA.
19. Known allergy to the study stent components, cobalt, nickel, chromium, molybdenum, Carbosil®, PBMA, polymer, or limus drugs (ridaforolimus, zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs or any other analogue or derivative or similar compounds).
20. Known allergy to protocol-required concomitant medications such as aspirin, or DAPT (clopidogrel, prasugrel, ticagrelor), or heparin and bivalirudin, or iodinated contrast that cannot be adequately pre-medicated.
21. 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).
22. Patient is participating in or plans to participate in any other investigational drug or device clinical trial that has not reached its primary endpoint.
23. Women who are pregnant or breastfeeding (women of child-bearing potential must have a negative pregnancy test within one week before treatment).
24. 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).
25. Patient has received an organ transplant or is on a waiting list for an organ transplant.
26. Patient is receiving or scheduled to receive chemotherapy within 30 days before or any time after the baseline procedure.
27. Patient is receiving oral or intravenous immunosuppressive therapy or has known life-limiting immunosuppressive or autoimmune disease (e.g., HIV). Corticosteroids are allowed.

    Angiographic Exclusion Criteria (visual estimate):
28. More than 100 mm length of planned stenting in the entire coronary tree.
29. Unprotected left main lesions ≥30%, or planned left main intervention.
30. Ostial LAD or LCX lesions (stenting of any diseased segment within 5 mm of the unprotected left main coronary artery).
31. Bifurcation lesions with planned dual stent implantation.
32. Stenting of lesions due to DES restenosis.
33. 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.

Primary outcomes:
measure: Device Success in the Target Lesion as Determined by the Angiographic Core Laboratory
timeFrame: during baseline procedure
Secondary outcomes:
measure: Target Lesion Success
timeFrame: during baseline procedure
measure: Procedure Success
timeFrame: during baseline procedure
Other outcomes:
measure: Major Adverse Cardiac Events (MACE)
timeFrame: Clinical follow-up will be performed at 30 days.
measure: Major Adverse Cardiac Events (MACE)
timeFrame: Telephone follow up will be performed at 6 months post procedure
measure: Major Adverse Cardiac Events (MACE)
timeFrame: Telephone follow up will be performed at 1 year post procedure
Locations:
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
Study officials:
affiliation: Rabin Medical Center
name: Abid Assali, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Souraski Medical Center
name: Shmuel Banai, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaplan Medical Center
name: Michael Jonas, MD
role: PRINCIPAL_INVESTIGATOR
References: