Angiography Study of BioNIR Drug Eluting Stent System (NIREUS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Medinol Ltd.
Sponsor:
Information provided by (Responsible Party):
Medinol Ltd.
ClinicalTrials.gov Identifier:
NCT01995500
First received: November 14, 2013
Last updated: August 17, 2014
Last verified: August 2014
  Purpose

The NIREUS study aims to demonstrate angiographic non-inferiority for the BioNIR Ridaforolimus Eluting Coronary Stent System (hereafter referred to as BioNIR) in comparison to the Resolute zotarolimus-eluting stent (hereafter referred to as Resolute).

The trial hypothesis is that the BioNIR is non-inferior to the Resolute for the primary endpoint of angiographic in-stent late loss at 6 months.


Condition Intervention Phase
Coronary Artery Stenosis
Device: BioNIR
Device: Resolute
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: BioNIR Ridaforolimus Eluting Coronary Stent System (BioNIR) EUropean Angiography Study

Further study details as provided by Medinol Ltd.:

Primary Outcome Measures:
  • In-stent late loss [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    In-stent late loss as measured by the angiographic core laboratory


Secondary Outcome Measures:
  • In-segment late loss [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    angiographic secondary endpoint

  • Follow-up percent diameter stenosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    angiographic: Follow-up percent diameter stenosis (in-stent and in-segment)

  • Binary restenosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    angiographic: Binary restenosis (in-stent and in-segment)

  • Length and patterns of angiographic restenosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    angiographic: Mehran classification

  • Device, Lesion, and Procedure Success [ Time Frame: Determined at time of baseline procedure ] [ Designated as safety issue: No ]

    Device success is defined as achievement of a final in-stent residual diameter stenosis of <50% (by QCA), using the assigned device only and without a device malfunction.

    Lesion success is defined as achievement of a final in-stent residual diameter stenosis of <50% (by QCA) using any percutaneous method.

    Procedure success is defined as achievement of a final in-stent diameter stenosis of <50% (by QCA) using the assigned device and/or with any adjunctive devices, without the occurrence of cardiac death, Q wave or non-Q wave MI, or repeat revascularization of the target lesion during the hospital stay.


  • Target lesion failure [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    Clinical: TLF, the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR

  • Major Adverse Cardiac Events (MACE) [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    Clinical: MACE, the composite rate of cardiac death, any MI or ischemia-driven TLR

  • Target vessel failure [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    TVF, the composite rate of death, target vessel-related MI, or ischemia-driven TVR

  • Overall Mortality [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    Clinical: Overall mortality during the trial period

  • Cardiac death [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    Clinical measure: The number of patients who suffered cardiac death

  • Myocardial Infarction [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    Clinical: myocardial infarction

  • Target vessel related MI [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    clinical: target vessel related MI

  • Ischemia driven TLR and TVR [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    clinical: TLR and TVR

  • Stent Thrombosis [ Time Frame: 30 days, 6 months, and 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    clinical: Stent Thrombosis (ARC definite and probable)


Estimated Enrollment: 300
Study Start Date: January 2014
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BioNIR

The BioNIR Ridaforolimus Eluting Coronary Stent System is a single use device/drug combination product comprising:

  • Stent - a mounted Cobalt Chromium (CoCr) alloy based stent
  • Delivery System - Rapid Exchange (RX) Coronary System
  • Polymer matrix coating - Poly n-butyl methacrylate (PBMA) and CarboSil®
  • Ridaforolimus drug - CAS Registry Number: 572924-54-0 The drug Ridaforolimus is utilized on the stent system at a dose of 1.1 μg/mm2 (with a drug load of 100 μg per 2.75/3.00 x 17 mm stent).
Device: BioNIR
drug-eluting stent
Active Comparator: Resolute

The Endeavor Resolute Zotarolimus-Eluting Coronary Stent System consists of four subsystems:

  • Endeavor Resolute Stent - a premounted cobalt alloy based stent
  • Delivery system - Rapid Exchange (RX) Coronary System
  • Polymer system
  • Zotarolimus - drug The Resolute has a nominal drug dose of 1.6 µg zotarolimus per mm2 of the stent surface area.
Device: Resolute
drug-eluting stent

Detailed Description:

This is a prospective, multi-center, single-blind, two-arm, 2:1 randomized clinical trial.

Randomization will be stratified by the presence of medically treated diabetes vs. no medically treated diabetes and by site. Lesions planned to be treated must be declared and recorded at time of randomization.

Angiographic follow-up will be performed at 6 months. Clinical follow-up will be performed at 30 days, 6 months, and 1, 2, 3, 4, and 5 years post randomization.

The Primary Endpoint is in-stent late loss at 6 months as measured by the angiographic core laboratory.

Angiographic Secondary Endpoints to be evaluated at 6 months are:

  • In-segment late loss
  • Follow-up percent diameter stenosis (in-stent and in-segment)
  • Binary restenosis (in-stent and in-segment)
  • Length and patterns of angiographic restenosis (Mehran classification)

Clinical Secondary Endpoints to be evaluated at 30 days, 6 months, and 1, 2, 3, 4 and 5 years, except as noted, are:

  • Device, Lesion, and Procedure Success at time of baseline procedure
  • Target lesion failure (TLF; the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR)
  • Major adverse cardiac events (MACE; the composite rate of cardiac death, any MI or ischemia-driven TLR)
  • Target vessel failure (TVF; the composite rate of death, target vessel-related MI, or ischemia-driven TVR)
  • Overall Mortality
  • Cardiac Death
  • Myocardial Infarction
  • Target Vessel Related MI
  • Ischemia-driven TLR
  • Ischemia-driven TVR
  • Stent Thrombosis (ARC definite and probable)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • 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 randomization and enzyme levels (CK-MB or Troponin) demonstrating that either or both enzyme levels have peaked.
  • Non-target vessel PCI are allowed prior to randomization depending on the time interval and conditions as follows:

    a. During Baseline Procedure: i. PCI of non-target vessels performed during the baseline procedure itself immediately prior to randomization 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.

    b. Less than 24 hours prior to Baseline Procedure: i. Not allowed (see exclusion criteria #3). c. 24 hours-30 days prior to Baseline Procedure: i. PCI of non-target vessels 24 hours to 30 days prior to randomization if successful and uncomplicated as defined above.

ii. 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.

d. Over 30 days prior to Baseline Procedure: iii. PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated.

  • 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):

  • Treatment of up to three de novo target lesions, maximum of one de novo target lesion per vessel
  • Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.25 mm and diameter stenosis ≥50% to <100%.
  • Lesion must be ≤28 mm long and can be covered by a single study stent with maximum length of 33 mm (note: multiple focal stenoses may be considered as a single lesion and be enrolled if they can be completely covered with one stent).
  • TIMI flow 2 or 3
  • If more than one target lesion will be treated, the RVD and lesion length of each must meet the above criteria.

Exclusion Criteria:

  • Planned procedures after the baseline procedure in either the target or non-target vessels.
  • 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.
  • PCI within the 24 hours preceding the baseline procedure and randomization.
  • Non-target lesion PCI in the target vessel within 12 months of the baseline procedure.
  • History of stent thrombosis.
  • 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.
  • Known LVEF <30%.
  • Subject is intubated.
  • Relative or absolute contraindication to DAPT for 12 months (including planned surgeries that cannot be delayed, or subject is indicated for chronic oral anticoagulant treatment).
  • Hemoglobin <10 g/dL.
  • Platelet count <100,000 cells/mm3 or >700,000 cells/mm3.
  • White blood cell (WBC) count <3,000 cells/mm3.
  • Clinically significant liver disease.
  • Renal disease as defined by an estimated creatinine clearance <40 mL/min using Cockcroft-Gault equation.
  • Active peptic ulcer or active bleeding from any site.
  • Bleeding from any site within the prior 8 weeks requiring active medical or surgical attention.
  • History of bleeding diathesis or coagulopathy or likely to refuse blood transfusions.
  • If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath.
  • Cerebrovascular accident or transient ischemic attack within the past 6 months, or any permanent neurologic defect attributed to CVA.
  • Known allergy to the study stent components, whether in the BioNIR or Resolute, e.g. cobalt, nickel, chromium, molybdenum, Carbosil®, PBMA, Biolinx polymer, or limus drugs (ridaforolimus, zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs or any other analogue or derivative or similar compounds).
  • 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.
  • 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).
  • Patient is participating in or plans to participate in any other investigational drug or device clinical trial that has not reached its primary endpoint.
  • Women who are pregnant or breastfeeding (women of child-bearing potential must have a negative pregnancy test within one week before treatment).
  • 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).
  • Patient has received an organ transplant or is on a waiting list for an organ transplant.
  • Patient is receiving or scheduled to receive chemotherapy within 30 days before or any time after the baseline procedure.
  • 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):

  • Unprotected left main lesions ≥30%, or planned left main intervention.
  • Stenting of ostial LAD or LCX lesions (stenting of any diseased segment within 5 mm of the unprotected left main coronary artery).
  • Lesions located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft.
  • Moderately or heavily calcified lesions.
  • Moderately or heavily tortuous or angulated lesions or vessels.
  • Bifurcation lesions in the presence of a side branch ≥2.0 mm in diameter.
  • Lesions containing thrombus.
  • Total occlusions.
  • In-stent restenotic lesions or lesions present within 10 mm of a previously implanted stent.
  • Lesions requiring pre-dilatation with any device other than simple balloon angioplasty (e.g. atherectomy or cutting/scoring balloons).
  • Another lesion in the target vessel is present that requires or has a high probability of requiring PCI during the baseline procedure or within 6 months after the baseline procedure.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01995500

Locations
Israel
Hadassah Hebrew University Medical Center Recruiting
Jerusalem, Israel, 91129
Contact: Haim Danenberg, MD    +972 2 6776564/3    danen@hadassah.org.il   
Sponsors and Collaborators
Medinol Ltd.
  More Information

No publications provided

Responsible Party: Medinol Ltd.
ClinicalTrials.gov Identifier: NCT01995500     History of Changes
Other Study ID Numbers: BioNIR-002
Study First Received: November 14, 2013
Last Updated: August 17, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Israel: Ministry of Health
Belgium: Ethics Committee
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Spain: Comité Ético de Investigación Clínica
Netherlands: Independent Ethics Committee
Poland: Ministry of Health

Keywords provided by Medinol Ltd.:
CAD
PCI
ACS
non ACS
BioNIR
DES

Additional relevant MeSH terms:
Coronary Stenosis
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Myocardial Ischemia
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014