SELUTION SLR™ 014 In-stent Restenosis (SELUTION4ISR)

SELUTION SLR™ 014 ISR: A Prospective Randomized Single Blind Multicenter Study to Assess the Safety and Effectiveness of the SELUTION SLR™ 014 Drug Eluting Balloon in the Treatment of Subjects With In-stent Restenosis

Prospective, multi-center, randomized, single blind, controlled, noninferiority clinical trial.

Subjects with previous bare-metal stent (BMS) or DES and qualifying evidence for ISR will be screened per the protocol inclusion and exclusion criteria. Eligible subjects will be randomized 1:1 to treatment with either the SELUTION SLR 014 DEB or SOC to include contemporary DES (zotarolimus-eluting stents [ZES] and everolimus-eluting stents [EES] only) or BA. A maximum of 20% of patients randomized to SOC will be treated with BA.

The primary endpoint will be Target Lesion Failure (TLF) at 12-months in the SOC group vs. the SELUTION SLR 014 DEB in all patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Restenosis
• Intervention / Treatment: Device: SELUTION SLR 014 DEB; Device: Standard of Care

Detailed Description

Prospective, multi-center, randomized, single blind, controlled, noninferiority clinical trial will enroll up to 418 randomized subjects (including up to 60 subjects in an angiographic and optical coherence tomography [OCT] sub-study) at up to 80 sites in the United States (US), Canada, Brazil, and Europe (EU). A minimum of 50% of the subjects will be enrolled in the US.

Subjects with previous bare-metal stent (BMS) or DES and qualifying evidence for ISR will be screened per the protocol inclusion and exclusion criteria. Eligible subjects will be randomized 1:1 to treatment with either the SELUTION SLR 014 DEB or SOC to include contemporary DES (zotarolimus-eluting stents [ZES] and everolimus-eluting stents [EES] only) or BA. A maximum of 20% of patients randomized to SOC will be treated with BA.

The primary endpoint will be Target Lesion Failure (TLF) at 12-months in the SOC group vs. the SELUTION SLR 014 DEB group.

A subset of up to 60 subjects will be enrolled in the angiographic and OCT sub-study and undergo planned angiographic and OCT follow-up within 30 days after completion of the 12-month primary endpoint clinical follow-up/assessment.

• Study Type: Interventional
• Enrollment (Actual): 418
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium
    • HartCentrum Hasslet, Jessa Ziekenhuis
• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04012-180
      • Instituto Dante Pazzanese de Cardiologia
    • São Paulo, São Paulo, Brazil, 05403-900
      • Instituto do Coração - São Paulo University
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences
• France
  • Dijon, France, 21000
    • Clinique Valmy
  • Massy, France, 91300
    • Hôpital privé Jacques Cartier
  • Rouen, France, 76000
    • Clinique Saint Hilaire
  • Toulouse, France, 31400
    • CHU Toulouse Rangueil
• Italy
  • Cotignola, Italy, 48033
    • Maria Cecilia Hospital
  • Milan, Italy, 20089
    • Instituto Clinico Humanitas Milan
  • Padua, Italy, 35128
    • Center Azienda Ospedaliero Universitaria de Padova
• Netherlands
  • AZ
    • Amsterdam, AZ, Netherlands, 1105
      • Amsterdam UMC, Academic Medical Centre
  • CX
    • Utrecht, CX, Netherlands, 3584
      • UMC Utrecht
  • GZ
    • Groningen, GZ, Netherlands, 9718
      • UMCG
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center
  • Colorado
    • Thornton, Colorado, United States, 80023
      • ClinRe 001-001
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Heart Institute
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health
    • Miami, Florida, United States, 33176
      • Baptist Cardiac & Vascular Institute
  • Georgia
    • Atlanta, Georgia, United States, 30033
      • Atlanta VA Medical Center
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Ascension St Vincents Heart Center
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Ascension Via Christi
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Centre, Harvard Medical School
  • Michigan
    • Kalamazoo, Michigan, United States, 49048
      • Ascension Borgess Heart Institute
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital
    • Southfield, Michigan, United States, 48075
      • Ascension St John Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • New Hampshire
    • Manchester, New Hampshire, United States, 03102
      • Manchester Catholic Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers, Robert Wood Johnson Medical School
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital & Heart Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Moses H. Cone Memorial Hospital
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17104
      • UPMC Pinnacle Health
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University Milton S. Hershey Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Cardiovascular Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • HCA Centennial
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor Scott & White
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
    • Temple, Texas, United States, 76508
      • Baylor Scott & White
  • Virginia
    • Richmond, Virginia, United States, 23225
      • HCA Chippenham/VA Cardiovascular Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Clinical Inclusion Criteria:

1. Subject age is ≥ 18 years or minimum legal age as required by local regulations.
2. Female subjects of childbearing potential have a negative pregnancy test ≤ 7 days before the procedure.
3. Subject presents with chronic coronary syndrome (CCS) (manifest as documented angina or positive functional testing), unstable angina or stabilized non-ST-elevation myocardial infarction (NSTEMI) (biomarkers stabilized or down trending) with an indication for percutaneous coronary intervention (PCI) and planned intervention.
4. Subject is eligible for dual antiplatelet therapy (DAPT) treatment with aspirin plus either Clopidogrel, Prasugrel, or Ticagrelor. Note: Subjects who require continued oral anticoagulant therapy my omit aspirin at discretion of investigator.
5. Life expectancy >1 year in opinion of investigator.
6. Subject is willing and able to provide informed consent and comply with study procedures and required follow-up evaluations.

Angiographic Inclusion Criteria

1. Target lesion is within a native coronary artery or major branch.
2. Target lesion is within a previously placed BMS or DES and does not extend further than 5 mm beyond either the proximal or distal edge of the stent.
3. Up to two (2) non-target lesions in non-target vessels may be treated, but successful PCI of the non-target lesions must be completed before treatment of the target lesion. Successful treatment is defined as no greater than 30% residual stenosis by visual estimate, no dissection greater than National Heart, Lung, Blood Institute (NHLBI) type C, and Thrombolysis in Myocardial Infarction (TIMI) grade flow in the non-target lesion > 2.
4. Target lesion is ≤ 26 mm in length.
5. Target lesion has diameter stenosis of > 50% and ≤ 99% by visual estimate.
6. Reference vessel diameter (RVD) is ≥ 2.00 mm and ≤ 4.50 mm.
7. Target lesion must be successfully pre-dilated/pre-treated. Note: Successful pre-dilation/pre-treatment is defined as dilation or pre-treatment that achieves stent expansion of approximately 80% of the distal RVD (at the discretion of the investigator) based on intravascular ultrasound (IVUS)/optical coherence tomography (OCT) and no greater than 30% residual stenosis by visual estimate and no dissection greater than NHLBI type C. TIMI grade flow in the target lesion must be > 2. Note: Atherectomy and cutting balloon are permitted for pre-treatment.

Clinical Exclusion Criteria:

1. Known hypersensitivity or allergy to Sirolimus or other pharmacologic agents required for the procedure.
2. ST-elevation myocardial infarction (STEMI) within 30 days.
3. Planned treatment of additional lesions in the target vessel, or more than two (2) non-target lesions within non-target vessels, during the index procedure.
4. Target lesion is located within a bifurcation with planned treatment of side branch vessel.
5. Target lesion is the 3rd or greater stent failure (i.e., more than two [2] layers of stent are present at any segment of the target lesion).
6. Target vessel had any previous vascular brachytherapy treatment or is planned to undergo brachytherapy at index procedure.
7. Previous PCI of the target vessel within 30 days.
8. Planned PCI of a non-target vessel, or a non-target lesion in the target vessel, within 30 days of randomization.
9. Subject has chronic renal insufficiency (dialysis dependent, or glomerular filtration rate [GFR] ≤ 30 ml/min/1.73 m² within 30 days of index procedure) or has undergone renal transplantation.
10. Subject has acute renal insufficiency confirmed by 50% increase of serum creatinine within 48 hours before procedure and/or decrease in urine output.
11. History of active peptic ulcer or gastrointestinal bleeding within prior 6 months or other inability to comply with recommended duration of DAPT.
12. Subject is pregnant, breast-feeding, or a woman of childbearing potential who is not using appropriate contraceptives to avoid becoming pregnant.
13. Documented left ventricular ejection fraction (LVEF) < 25%.
14. Currently participating in another investigational drug or device study that has not completed primary endpoint follow-up.

Angiographic Exclusion Criteria

1. Target lesion is a total occlusion or has evidence of thrombus.
2. Target lesion involves an unprotected left main.
3. Target lesion has > 30% residual stenosis by visual estimate or dissection greater than NHLBI type C after pre-dilation/pre-treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SELUTION SLR 014 DEB; The SELUTION Sustained Limus Release (SLR)™ 014 drug-eluting balloon (DEB) catheter is a combination product consisting of a standard percutaneous transluminal angioplasty (PTA) balloon catheter coated with a drug (Sirolimus).	Device: SELUTION SLR 014 DEB; The SELUTION Sustained Limus Release (SLR)™ 014 drug-eluting balloon (DEB) catheter is a combination product consisting of a standard percutaneous transluminal angioplasty (PTA) balloon catheter coated with a drug (Sirolimus).
Active Comparator: Standard Of Care; POBA or FDA-approved commercially available -limus eluting DES	Device: Standard of Care; POBA or FDA-approved commercially available -limus eluting DES

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Target Lesion Failure (TLF)	12 months post-index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device success		Index Procedure
Lesion Success		Index Procedure
Procedure Success		Index Procedure
Composite Safety Endpoint		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
All-cause Mortality		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
Cardiovascular Mortality		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
MI		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
Clinically driven TLR, all TLR		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
Clinically driven TVR, all TVR, non-TVR		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
TLF		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
TVF		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
Stent Thrombosis		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
Bleeding		Prior to discharge, at 1, 6, and 12 months
Net adverse clinical events		Prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up
Binary angiographic restenosis		12 months
In-stent percent diameter stenosis		12 months
In-segment percent diameter stenosis		12 months
In-stent LLL		12 months
In-segment LLL		12 months
In-stent MLD		12 months
In-segment MLD		12 months
OCT assessment of neointimal hyperplasia, neo-atherosclerosis, and stent malapposition		12 months
TLF	SELUTION SLR 014 DEB versus DES among participants with one previous layer of stent	12 months

Other Outcome Measures

Outcome Measure	Time Frame
Cardiac Biomarker Elevations	Peri-Procedural

Collaborators and Investigators

• Sponsor: M.A. Med Alliance S.A.
• Collaborators: IQVIA Pty Ltd; Cordis US Corp.
• Investigators: Principal Investigator: Donald E Cutlip, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Cutlip DE, Mehran R, Doros G, Kaplinskiy V, Lee J, Zheng L, Kausik M, Osborn E, Waksman R. Prospective randomized single-blind multicenter study to assess the safety and effectiveness of the SELUTION SLR 014 drug eluting balloon in the treatment of subjects with in-stent restenosis: Rationale and design. Am Heart J. 2025 Jun;284:11-19. doi: 10.1016/j.ahj.2025.02.001. Epub 2025 Feb 12.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2020
• Primary Completion (Actual): August 15, 2025
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: February 19, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 21, 2020

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Coronary; Drug Eluting Balloon; In-stent restenosis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Coronary Stenosis; Coronary Restenosis
• Other Study ID Numbers: SEL-003-2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes