EluNIR Ridaforolimus Eluting Coronary Stent System in Patients at High Bleeding Risk (HBR)- EluNIR HBR Study

The study will enroll approximately 316 subjects with a wide spectrum of PCI indications (stable angina as well as ACS), who are considered to be at high risk of bleeding. Patients will undergo PCI with implantation of the EluNIR stent, followed by shortened duration (1 months in stable patients, and up to 3 months in ACS patients) of DAPT.

Study Overview

• Status: Completed
• Conditions: Coronary Stenosis
• Intervention / Treatment: Device: Percutaneous Coronary Intervention (PCI)

Detailed Description

This is a prospective, multi-center (Up to 20 sites), single-arm, open-label post marketing clinical trial.

The objectives: To assess the safety and efficacy of shortened DAPT duration (30 days in stable patients and up to 90 days in ACS patients) following PCI using the EluNIR stent, in patients considered to be at high bleeding risk (HBR).

Patients will be enrolled to the study prior to the PCI procedure.Once a patient has signed an informed consent, met all general and angiographic eligibility criteria, and a guidewire has successfully been passed beyond the target lesion and lesion preparation (if indicated) completed, the patient will be enrolled into the trial.Data collection commences after the subject has signed the informed consent form. Data collection including subject demographic information, laboratory tests, and procedural data as well as follow-up visits or telephone contacts will be captured by the Investigator or site coordinator who has been trained on the CIP and Case Report Forms (CRF).

After discharge from the hospital, each subject will be followed with an in-clinic follow-up visit at 30 days, and follow-up by phone at 6 months and 1year post procedure. Patients with recurrent ischemic events within the first 30 days as well as patients in whom the initial presentation was ACS and in whom the investigator has decided to continue DAPT beyond 30 days will have an additional phone follow-up at 3 months.

The clinical investigation will last for the expected duration of each subject's participation.

Each subject will remain in the clinical investigation for approximately 1 year from the time of the study stent implantation until the last follow-up telephone contact.

The trial population will consist of approximately 316 male and female subjects undergoing PCI for angina (stable or unstable), silent ischemia, non-ST elevation MI (NSTEMI) considered at HBR.

• Study Type: Observational
• Enrollment (Actual): 319

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel
    • Medinol LTD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

High bleeding risk subjects undergoing PCI using the EluNIR stent for angina, silent ischemia or non STEMI.

Description

Inclusion Criteria:

All inclusion criteria must be present for the patient to be eligible for enrollment.

General Inclusion Criteria

1. Age ≥ 18 years.
2. Patient with angina (stable or unstable), silent ischemia or NSTEMI, undergoing PCI using the EluNIR stent.
3. Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule.

In addition, patients must meet at least one of the following criteria for high risk of bleeding:

1. Age ≥75 years
2. Oral anticoagulation planned to continue after PCI
3. Hemoglobin <11 g/liter or anemia requiring transfusion within 12 weeks before enrollment to the study
4. Platelet count< 100,000/mm³
5. Hospital admission for bleeding in previous 12 months
6. Stroke in previous 12 months
7. Previous intracerebral hemorrhage
8. Severe chronic liver disease defined as patients who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy or jaundice
9. Renal failure defined as creatinine clearance< 40 ml/min
10. Non-skin cancer diagnosed or treated < 3 years
11. Planned surgery within 12 months that would require interruption of DAPT
12. Planned daily NSAID (other than aspirin) or steroids for > 30 days after PCI
13. Expected nonadherence to >30 days of dual antiplatelet therapy in stable patients and >3 months in ACS patients

Angiographic inclusion criteria (visual estimate)

1. 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, bifurcation lesions (except planned dual stent implantation), ostial RCA lesions, tortuous lesions, bare metal stent restenotic lesions, protected left main lesions, and saphenous vein graft lesions.
2. Up to 2 overlapping stents are allowed (ie, one overlap)

Exclusion Criteria:

All exclusion criteria must be absent for the patient to be eligible for enrollment.

General Exclusion Criteria

1. Pregnant and breastfeeding women
2. Patients requiring a planned staged PCI with a non-study stent
3. Patients expected not to comply with 1-month DAPT.
4. Patients expected not to comply with long-term single anti-platelet therapy
5. PCI during the previous 12 months with a non-study stent
6. History of stent thrombosis
7. 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.
8. Subject is intubated.
9. Known LVEF <30%.
10. White blood cell (WBC) count <3,000 cells/mm3.
11. Active bleeding from any site at time of inclusion
12. 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.
13. Any co-morbid condition that may cause non-compliance with the protocol (e.g. dementia, substance abuse, etc.) or reduced life expectancy to <12 months (e.g. cancer, severe heart failure, severe lung disease).
14. Patient has received an organ transplant or is on a waiting list for an organ transplant.
15. Participation in another clinical trial that has not reached its primary endpoint.

Angiographic Exclusion Criteria (visual estimate)

1. Visually estimated RVD<2.5 mm or >4.25mm.
2. Unprotected left main intervention.
3. Ostial LAD and/or LCx intervention
4. Bifurcation lesions with dual stent implantation.
5. Stenting of lesions due to DES restenosis.
6. Total stented length > 60 mm
7. Planned implantation of any DES which is not EluNIR

Note: In case the procedure required the unplanned implantation of a different (non-EluNIR) stent the subject will be de-registered from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ACS and Non-ACS; DAPT will be stopped at 30 days in non-ACS subjects while at ACS Patients it may be maintained for up to 3 months. In patients with ACS or with an ischemic event during the first 30 days, DAPT may be continued at the discretion of the investigator. In ACS patients DAPT should be continued for a maximum of 3 months. For patients with recurrent ischemic events duration of DAPT therapy will be at the discretion of the investigator. Patients receiving long-term oral anticoagulation with either a Vitamin K inhibitor or a NOAC/DOAC will receive either single antiplatelet therapy with clopidogrel, or DAPT for 30 days (triple therapy) followed by single antiplatelet therapy with clopidogrel. Clopidogrel (75 mg QD) will be given to these patients post procedure for 6 months in stable patients and 12 months in ACS patients.

Device: Percutaneous Coronary Intervention (PCI); Patients enrolled to the study will undergo angiography followed by PCI according to current guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year (ARC definite and probable)	1 Year

Secondary Outcome Measures

Outcome Measure	Time Frame
TLF, defined as the composite of cardiac death, target vessel-related MI, or ischemia-driven TLR.	To be evaluated at 30 days, 6 months, and 1 year
Major adverse cardiac events (MACE; the composite rate of cardiac death, any MI or ischemia-driven TLR)	To be evaluated at 30 days, 6 months, and 1 year
Target vessel failure (TVF; the composite rate of death, target vessel related MI or ischemia-driven TVR)	To be evaluated at 30 days, 6 months, and 1 year
The composite of cardiac death, myocardial infarction, or stent thrombosis at 30 days and 6 months	To be evaluated at 30 days, 6 months, and 1 year
All-cause mortality	To be evaluated at 30 days, 6 months, and 1 year
Cardiac death	To be evaluated at 30 days, 6 months, and 1 year
Bleeding events according to BARC definitions	To be evaluated at 30 days, 6 months, and 1 year
Myocardial Infarction	To be evaluated at 30 days, 6 months, and 1 year
Target Vessel Related MI	To be evaluated at 30 days, 6 months, and 1 year
Ischemia-driven TLR	To be evaluated at 30 days, 6 months, and 1 year
Ischemia-driven TVR	To be evaluated at 30 days, 6 months, and 1 year
Stent Thrombosis (ARC definite and probable)	To be evaluated at 30 days, 6 months, and 1 year
Bleeding complications (BARC definitions), evaluated as components and as a composite of BARC Type 3 and 5 bleeding	To be evaluated at 30 days, 6 months, and 1 year

Collaborators and Investigators

• Sponsor: Medinol Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 6, 2019
• Primary Completion (ACTUAL): June 10, 2021
• Study Completion (ACTUAL): June 10, 2021

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (ACTUAL): March 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: PCI; bleeding
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Hemorrhage; Coronary Stenosis
• Other Study ID Numbers: EluNIR HBR study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes