Clinical trial NCT02828917: MedJ-01 Ridaforolimus Eluting Coronary Stent System Trial (JNIR)
Official title: Multi-center Study for Evaluating the Safety and Efficacy of the MedJ-01 Ridaforolimus Eluting Coronary Stent System (MedJ-01) In Coronary Stenosis Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: de Novo or Restenosis Lesions
Lead sponsor: Medinol Ltd.
Sponsor class: INDUSTRY
First posted: 2016-07-12
Enrollment: 104
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: MedJ-01 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) Coronary System Delivery System
* A Poly n-butyl methacrylate (PBMA) and CarboSil®Polymer matrix coating
* Ridaforolimus drug - CAS Registry Number: 572924-54-0 MedJ-01 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.

JNIR01 is aimed at assessing TLF at one year with the MedJ-01 stent in a Japanese patient population to show equivalence to the results of the BIONICS Trial.

Detailed description: This study aims to evaluate MedJ-01 safety and efficacy for de novo or restenosis lesion with target vessel diameter of 2.5mm to 4.25, for subjects undergoing coronary artery stent implantation. The target population is subjects undergoing PCI for 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, and recent subacute STEMI (\>72 hours from initial presentation and stable). Complex lesions are allowed. A maximum of two target vessels and two lesions per vessel may be treated (two lesions separated by up to 10 mm that can be covered by a single stent are considered as one lesion); the total planned study stenting in the coronary tree cannot exceed 100 mm.

Eligibility criteria: Inclusion Criteria:

1. Patient with indication for PCI including angina (stable/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 subacute STEMI. For subacute STEMI the time of presentation to the first treating hospital, whether a transfer facility or the study hospital, must be \>72 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 criterion #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 vessel 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:
     * PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated.
3. Patient 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 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 that is non-occlusive and does not require thrombectomy, CTO, bifurcationlesions (except planned dual stent implantation), ostial RCA lesions, tortuous lesions, bare metal stent restenotic lesions, protected left main lesions.
6. Overlapping stents are allowed with the investigational device (MedJ-01).

Exclusion Criteria:

1. STEMI within 72 hours (subacute) 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 12 months (including planned surgeries that cannot be delayed)
9. Subject has an indication for chronic oral anticoagulant treatment (with either vitamin K antagonists or novel anticoagulants - NOACs)
10. Calculated creatinine clearance \<30 mL/min using Cockcroft-Gault equation.
11. Hemoglobin \<10 g/dL.
12. Platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3.
13. White blood cell (WBC) count \<3,000 cells/mm3.
14. Clinically significant liver disease.
15. Active peptic ulcer or active bleeding from any site.
16. Bleeding from any site within the prior 8 weeks requiring active medical or surgical attention.
17. If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath.
18. History of bleeding diathesis or coagulopathy or will refuse blood transfusions.
19. Cerebrovascular accident or transient ischemic attack within the past 6 months, or any permanent neurologic defect attributed to CVA.
20. Known allergy to the study stent components e.g. cobalt, nickel, chromium, Carbosil®, PBMA, or limus drugs (ridaforolimus, zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs or any other analogue or derivative or similar compounds).
21. Known allergy to protocol-required concomitant medications such as aspirin, or DAPT (Drugs that inhibit P2Y12 such as clopidogrel and prasugrel), or heparin, or iodinated contrast that cannot be adequately pre-medicated.
22. 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).
23. Patient is participating in any other investigational drug or device clinical trial that has not reached its primary endpoint, or plans to participate in any clinical trial.
24. Women who are pregnant or breastfeeding (women of child-bearing potential, defined as females of childbearing potential if they have not undergone a permanent contraceptive operation or they are not postmenopausal, must have a negative pregnancy test within one week before treatment. Permanent contraceptive operation is defined as: hysterectomy, hysterosalpingectomy, or bilateral oophorectomy. The status of a female should be considered as postmenopausal when she has not had a period for 12 consecutive months without an alternative medical cause).
25. 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).
26. Patient has received an organ transplant or is on a waiting list for an organ transplant.
27. Patient is receiving or scheduled to receive chemotherapy within 30 days before or any time after the baseline procedure.
28. 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):
29. Target lesions in more than two (2) major coronary arteries (i.e., two of LAD, LCX, RCA) and their respective branches (the Ramus Intermedius is defined as a branch of the LCX).
30. More than two target lesions per target vessel are planned (two lesions separated by less than 10 mm that can be covered by a single stent are considered as one lesion).
31. More than 100 mm length of planned study stenting in the entire coronary tree.
32. Occlusive thrombus and/or a thrombus requiring thrombectomy in a target vessel.
33. Unprotected left main lesions ≥30%, or planned unprotected left main intervention.
34. Ostial LAD or LCX lesions (stenting of any diseased segment within 5 mm of the unprotected left main coronary artery).
35. Bifurcation lesions with planned dual stent implantation.
36. Stenting of lesions due to DES restenosis.
37. 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.
38. Target lesion exists in bypass graft vessels.

Primary outcomes:
measure: Target Lesion Failure (TLF)
timeFrame: 12 months
Secondary outcomes:
measure: Device Success at Time of Baseline Procedure
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Lesion Success at Time of Baseline Procedure
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Procedure Success at Time of Baseline Procedure
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: TLF
timeFrame: 30 days, 6 months, and 2, 3, 4 and 5 years
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Target Vessel Failure (TVF)
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: All-cause Mortality
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Cardiac Death
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Myocardial Infarction
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Target Vessel Related MI
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Ischemia-driven TLR
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Ischemia-driven TVR
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
measure: Stent Thrombosis
timeFrame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years
Other outcomes:
Locations:
city: Kamakura-City
country: Japan
facility: Shonan Kamakura General
state: Kanagawa
Study officials:
affiliation: Shonan Kamakura General Hospital
name: Shigeru Saito, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sapporo Higashi Tokushukai Hospital
name: Seiji Yamazaki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kanto Rosai Hospital
name: Atsuo Namiki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Miyazaki Medical Association Hospital
name: Yoshisato Shibata, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Higashi Takarazuka Satoh Hospital
name: Satoru Otsuji, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kyoto Katsura Hospital
name: Shigeu Nakamura, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Takahashi Hospital
name: Akihiko Takahashi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shin Koga Hospital
name: Tomohiro Kawasaki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Hakodate Hokkaido
name: Yasuhiro Makita, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Saiseikai Fukuoka General Hospital
name: Takeshi Serikawa, MD
role: PRINCIPAL_INVESTIGATOR
References: