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Study of BioNIR Drug Eluting Stent System in Coronary Stenosis (BIONICS)

Primary Purpose

Coronary Artery Stenosis

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
BioNIR
Resolute
Sponsored by
Medinol Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Stenosis focused on measuring more comers, DES, BioNIR, ACS, non ACS, complex lesions

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient with indication for PCI including angina/silent ischemia/NSTEMI/recent STEMI
  • Non-target vessel PCI allowed prior to randomization depending on time interval and certain conditions
  • Patient/legal guardian willing & able to provide informed written consent & comply with follow-up visits & testing schedule
  • Target lesion(s) must be located in native coronary artery/bypass graft conduit w/visually estimated diameter ≥2.5mm to ≤4.25mm.
  • Complex lesions allowed, including calcified, presence of thrombus, CTO, bifurcation (except as per exclusion criteria #30), ostial RCA, tortuous, bare metal stent restenotic, protected left main, and saphenous vein graft

Exclusion Criteria:

  • STEMI within 24 hours of init. time of presentation to first treating hospital, or in whom enzyme levels (either CK-MB or Troponin) have not peaked
  • PCI within 24 hours preceding baseline procedure
  • Non-target lesion PCI in target vessel within 12 months of baseline procedure
  • History of stent thrombosis
  • Cardiogenic shock (persistent hypotension [systolic blood pressure <90mm/Hg for MT 30 min] or requiring pressors/hemodynamic support, including IABP)
  • Subject is intubated
  • Known LVEF <30%
  • Relative/absolute contraindication to DAPT for 12 months (including planned surgeries that cannot be delayed, or subject indicated for chronic oral anticoagulant treatment)
  • Calculated creatinine clearance <30 mL/min per Cockcroft-Gault equation (<40mL/min for subjects participating in angiographic follow-up sub-study)
  • Hemoglobin <10g/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
  • Active peptic ulcer/active bleeding from any site
  • Bleeding from any site within prior 8 wks requiring active medical/surgical attention
  • If femoral access is planned, significant peripheral arterial disease that precludes safe insertion of 6F sheath
  • History of bleeding diathesis/coagulopathy/will refuse blood transfusions
  • Cerebrovascular accident/transient ischemic attack within past 6 months, or any permanent neurologic defect attributed to CVA
  • Known allergy to study stent components, BioNIR or Resolute
  • Known allergy to protocol-required concomitant medications: aspirin/DAPT (clopidogrel, prasugrel, ticagrelor)/heparin and bivalirudin/iodinated contrast that cannot be adequately pre-medicated
  • Any co-morbid condition that may cause non-compliance with protocol (e.g. dementia, substance abuse) /reduced life expectancy to <24 months (e.g. cancer, severe heart failure, severe lung disease)
  • Patient participating/plans to participate in another investigational drug/device clinical trial that has not reached its primary endpoint
  • Pregnant/breastfeeding women (women of child-bearing potential must have a negative pregnancy test within 1 wk before treatment)
  • Women who intend to become pregnant within 12 months after baseline procedure (sexually active women of child-bearing potential must agree to use a reliable method of contraception from time of screening through 12 months post baseline procedure)
  • Patient has received/is on a waiting list for an organ transplant
  • Patient receiving/scheduled to receive chemotherapy within 30 days before/any time after the baseline procedure
  • Patient receiving oral/intravenous immunosuppressive therapy or has known life-limiting immunosuppressive/autoimmune disease (e.g. HIV); corticosteroids are allowed
  • More than 100mm length of planned stenting in the entire coronary tree
  • Unprotected left main lesions ≥30%, or planned left main intervention
  • Ostial LAD/LCX lesions (stenting of any diseased segment within 5mm of the unprotected left main coronary artery)
  • Bifurcation lesions with planned dual stent implantation
  • Stenting of lesions due to DES restenosis
  • Another lesion in a target/non-target vessel (including all side branches) is present that requires/has high probability of requiring PCI within 12 months after baseline procedure

Sites / Locations

  • Piedmont Healthcare
  • ZNA Middelheim
  • Queen Elizabeth II Health Sciences Centre
  • Hadassah Hebrew University Medical Center
  • San Raffaele Hospital
  • Maasstad Ziekenhuis
  • PAKS, II Oddzial Kardiologiczny
  • Hospital Meixoeiro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

BioNIR

Resolute

Arm Description

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).

The Endeavor Resolute Zotarolimus-Eluting Stent System consists of four subsystems: Endeavor Resolute Stent- a pre-mounted cobalt alloy based stent Delivery system (Rapid Exchange [RX] Coronary System) Polymer system Zotarolimus - drug The Resolute has a nominal drug dose of 1.6µg Zotarolimus per mm2 of the stent surface area.

Outcomes

Primary Outcome Measures

Target Lesion Failure (TLF)
The primary endpoint of TLF at 12 months was defined as the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR.

Secondary Outcome Measures

Device Success
Clinical: Acute secondary endpoint determined at time of baseline procedure
TLF
Clinical secondary endpoint to be evaluated at 30 days, 6 months, and 2, 3, 4 and 5 years, defined as the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR
Major Adverse Cardiac Events
Clinical: MACE; the composite rate of cardiac death, any MI or ischemia-driven TLR
Target Vessel Failure
Clinical: TVF; the composite rate of death, target vessel related MI or ischemia-driven TVR
All Cause Mortality
Clinical: The number of patients who die from all causes
Cardiac Death
Clinical: The number of patients who die of cardiac-related causes
Myocardial Infarction
Clinical: The number of patients who suffer a myocardial infarction.
Target Vessel Related MI
Clinical: The number of patients who suffer a MI that is related to the target vessel of the procedure.
Ischemia Driven TLR
Clinical:
Ischemia Driven TVR
Clinical:
Stent Thrombosis
Clinical: ARC definite and probable
Angiographic Sub-Study: In-stent and In-segment Late Loss
Secondary Endpoint for angiographic in-stent and in-segment late loss
IVUS Sub-Study: In-stent Percent Neointimal Hyperplasia
IVUS: In-stent percent neointimal hyperplasia
IVUS Sub-Study: Stent Mal-apposition
IVUS Sub-Study: Stent mal-apposition
Lesion Success
Measures whether the lesion was successfully treated.
Procedure Success
Acute clinical endpoint: The success of the procedure as determined at time of baseline procedure

Full Information

First Posted
November 12, 2013
Last Updated
October 1, 2023
Sponsor
Medinol Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT01995487
Brief Title
Study of BioNIR Drug Eluting Stent System in Coronary Stenosis
Acronym
BIONICS
Official Title
BioNIR Ridaforolimus Eluting Coronary Stent System (BioNIR) In Coronary Stenosis Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
August 28, 2016 (Actual)
Study Completion Date
November 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medinol Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The BioNIR study aims to show that the BioNIR ridaforolimus eluting stent is non-inferior to the Resolute zotarolimus-eluting stent for the primary clinical endpoint of target lesion failure (TLF) at 12 months; that it is non-inferior to the Resolute for the secondary endpoint of angiographic in-stent late loss at 13 months; and that it is more cost-effective.
Detailed Description
The BioNIR is a prospective, multi-center, single-blind, two-arm, randomized clinical trial. The population will consist of subjects undergoing PCI for angina (stable or unstable), silent ischemia, NSTEMI, and recent STEMI. Complex lesions are allowed. There is no limit to the number of lesions per vessel or individual lesion length; however, the total planned stenting in the coronary tree cannot exceed 100mm. Randomization will be stratified by the presence of medically treated diabetes vs. no medically treated diabetes, acute coronary syndrome (ACS) vs. non-ACS, and by site. Lesions planned to be treated must be declared and recorded at time of randomization. Planned staged procedures, if necessary, must be declared immediately post procedure. Clinical follow-up will be performed at 30 days, 6 months, and 1, 2, 3, 4, and 5 years post randomization. 200 patients at participating North American sites will be consented for planned angiographic follow-up at 13 months after enrollment, with 100 of these patients consented to undergo planned IVUS at baseline and at 13 months following randomization. The primary endpoint is Target Lesion Failure (TLF) at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. Clinical Secondary Endpoints to be evaluated at 30 days, 6 months, and 1, 2, 3, 4 and 5, except as noted: Device, Lesion, and Procedure Success at time of baseline procedure TLF at 30 days, 6 months, and 2, 3, 4 and 5 years defined as 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) All-cause mortality Cardiac death Myocardial Infarction Target Vessel Related MI Ischemia-driven TLR Ischemia-driven TVR Stent Thrombosis (ARC definite and probable) Angiographic Sub-Study Secondary Endpoint to be evaluated at 13 months: • Angiographic in-stent and in-segment late loss IVUS Sub-Study Secondary Endpoint to be evaluated at 13 months: In-stent percent neointimal hyperplasia Stent mal-apposition A key component of this trial will be a prospective assessment of health care resource utilization, costs and cost effectiveness. A separate cost effectiveness assessment plan describes the data collection and analysis. Sample Size Consideration: From recent US trials of best in class DES (Xience V, Promus Element and Resolute), the 1-year TLF rate in patients with non-complex lesions not undergoing routine angiographic follow-up is approximately 3.8%. Using the assumption of the more-comers' design, the 1-year event rate will be conservatively increased by 50% (assuming enrollment rate for complex patients/lesions is 50% with double the standard event rate) - thus 5.8%. Therefore, with a one-sided 95% upper bound of the confidence interval of 3.3% (a relative 57% margin) and 1:1 randomization, enrolling 1810 patients (905 per group) provides 90% power to demonstrate non-inferiority. Assuming 95% follow-up rate at 1 year, approximately 1906 patients will be enrolled (953 in each group).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Stenosis
Keywords
more comers, DES, BioNIR, ACS, non ACS, complex lesions

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a Drug-Device combination Product.
Masking
Participant
Allocation
Randomized
Enrollment
1919 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BioNIR
Arm Type
Experimental
Arm Description
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).
Arm Title
Resolute
Arm Type
Active Comparator
Arm Description
The Endeavor Resolute Zotarolimus-Eluting Stent System consists of four subsystems: Endeavor Resolute Stent- a pre-mounted cobalt alloy based stent Delivery system (Rapid Exchange [RX] Coronary System) Polymer system Zotarolimus - drug The Resolute has a nominal drug dose of 1.6µg Zotarolimus per mm2 of the stent surface area.
Intervention Type
Device
Intervention Name(s)
BioNIR
Intervention Description
drug-eluting stent
Intervention Type
Device
Intervention Name(s)
Resolute
Intervention Description
drug-eluting stent
Primary Outcome Measure Information:
Title
Target Lesion Failure (TLF)
Description
The primary endpoint of TLF at 12 months was defined as the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Device Success
Description
Clinical: Acute secondary endpoint determined at time of baseline procedure
Time Frame
Determined at time of baseline procedure
Title
TLF
Description
Clinical secondary endpoint to be evaluated at 30 days, 6 months, and 2, 3, 4 and 5 years, defined as the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Major Adverse Cardiac Events
Description
Clinical: MACE; the composite rate of cardiac death, any MI or ischemia-driven TLR
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Target Vessel Failure
Description
Clinical: TVF; the composite rate of death, target vessel related MI or ischemia-driven TVR
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
All Cause Mortality
Description
Clinical: The number of patients who die from all causes
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Cardiac Death
Description
Clinical: The number of patients who die of cardiac-related causes
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Myocardial Infarction
Description
Clinical: The number of patients who suffer a myocardial infarction.
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Target Vessel Related MI
Description
Clinical: The number of patients who suffer a MI that is related to the target vessel of the procedure.
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Ischemia Driven TLR
Description
Clinical:
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Ischemia Driven TVR
Description
Clinical:
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Stent Thrombosis
Description
Clinical: ARC definite and probable
Time Frame
30 days, 6 months, and 1, 2, 3, 4 and 5 years
Title
Angiographic Sub-Study: In-stent and In-segment Late Loss
Description
Secondary Endpoint for angiographic in-stent and in-segment late loss
Time Frame
13 months
Title
IVUS Sub-Study: In-stent Percent Neointimal Hyperplasia
Description
IVUS: In-stent percent neointimal hyperplasia
Time Frame
13 months
Title
IVUS Sub-Study: Stent Mal-apposition
Description
IVUS Sub-Study: Stent mal-apposition
Time Frame
13 months
Title
Lesion Success
Description
Measures whether the lesion was successfully treated.
Time Frame
Determined at time of baseline procedure
Title
Procedure Success
Description
Acute clinical endpoint: The success of the procedure as determined at time of baseline procedure
Time Frame
Determined at time of baseline procedure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with indication for PCI including angina/silent ischemia/NSTEMI/recent STEMI Non-target vessel PCI allowed prior to randomization depending on time interval and certain conditions Patient/legal guardian willing & able to provide informed written consent & comply with follow-up visits & testing schedule Target lesion(s) must be located in native coronary artery/bypass graft conduit w/visually estimated diameter ≥2.5mm to ≤4.25mm. Complex lesions allowed, including calcified, presence of thrombus, CTO, bifurcation (except as per exclusion criteria #30), ostial RCA, tortuous, bare metal stent restenotic, protected left main, and saphenous vein graft Exclusion Criteria: STEMI within 24 hours of init. time of presentation to first treating hospital, or in whom enzyme levels (either CK-MB or Troponin) have not peaked PCI within 24 hours preceding baseline procedure Non-target lesion PCI in target vessel within 12 months of baseline procedure History of stent thrombosis Cardiogenic shock (persistent hypotension [systolic blood pressure <90mm/Hg for MT 30 min] or requiring pressors/hemodynamic support, including IABP) Subject is intubated Known LVEF <30% Relative/absolute contraindication to DAPT for 12 months (including planned surgeries that cannot be delayed, or subject indicated for chronic oral anticoagulant treatment) Calculated creatinine clearance <30 mL/min per Cockcroft-Gault equation (<40mL/min for subjects participating in angiographic follow-up sub-study) Hemoglobin <10g/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 Active peptic ulcer/active bleeding from any site Bleeding from any site within prior 8 wks requiring active medical/surgical attention If femoral access is planned, significant peripheral arterial disease that precludes safe insertion of 6F sheath History of bleeding diathesis/coagulopathy/will refuse blood transfusions Cerebrovascular accident/transient ischemic attack within past 6 months, or any permanent neurologic defect attributed to CVA Known allergy to study stent components, BioNIR or Resolute Known allergy to protocol-required concomitant medications: aspirin/DAPT (clopidogrel, prasugrel, ticagrelor)/heparin and bivalirudin/iodinated contrast that cannot be adequately pre-medicated Any co-morbid condition that may cause non-compliance with protocol (e.g. dementia, substance abuse) /reduced life expectancy to <24 months (e.g. cancer, severe heart failure, severe lung disease) Patient participating/plans to participate in another investigational drug/device clinical trial that has not reached its primary endpoint Pregnant/breastfeeding women (women of child-bearing potential must have a negative pregnancy test within 1 wk before treatment) Women who intend to become pregnant within 12 months after baseline procedure (sexually active women of child-bearing potential must agree to use a reliable method of contraception from time of screening through 12 months post baseline procedure) Patient has received/is on a waiting list for an organ transplant Patient receiving/scheduled to receive chemotherapy within 30 days before/any time after the baseline procedure Patient receiving oral/intravenous immunosuppressive therapy or has known life-limiting immunosuppressive/autoimmune disease (e.g. HIV); corticosteroids are allowed More than 100mm length of planned stenting in the entire coronary tree Unprotected left main lesions ≥30%, or planned left main intervention Ostial LAD/LCX lesions (stenting of any diseased segment within 5mm of the unprotected left main coronary artery) Bifurcation lesions with planned dual stent implantation Stenting of lesions due to DES restenosis Another lesion in a target/non-target vessel (including all side branches) is present that requires/has high probability of requiring PCI within 12 months after baseline procedure
Facility Information:
Facility Name
Piedmont Healthcare
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
ZNA Middelheim
City
Antwerp
Country
Belgium
Facility Name
Queen Elizabeth II Health Sciences Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 3A7
Country
Canada
Facility Name
Hadassah Hebrew University Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
San Raffaele Hospital
City
Milan
ZIP/Postal Code
20162
Country
Italy
Facility Name
Maasstad Ziekenhuis
City
Rotterdam
ZIP/Postal Code
3079 DZ
Country
Netherlands
Facility Name
PAKS, II Oddzial Kardiologiczny
City
Bielsko-biala
ZIP/Postal Code
43-316
Country
Poland
Facility Name
Hospital Meixoeiro
City
Pontevedra
State/Province
Vigo
ZIP/Postal Code
36200
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
28794001
Citation
Kandzari DE, Smits PC, Love MP, Ben-Yehuda O, Banai S, Robinson SD, Jonas M, Kornowski R, Bagur R, Iniguez A, Danenberg H, Feldman R, Jauhar R, Chandna H, Parikh M, Perlman GY, Balcells M, Markham P, Ozan MO, Genereux P, Edelman ER, Leon MB, Stone GW. Randomized Comparison of Ridaforolimus- and Zotarolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: Primary Results From the BIONICS Trial (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis). Circulation. 2017 Oct 3;136(14):1304-1314. doi: 10.1161/CIRCULATIONAHA.117.028885. Epub 2017 Aug 9.
Results Reference
derived

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Study of BioNIR Drug Eluting Stent System in Coronary Stenosis

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