SELUTION4SFA Trial

Not Applicable

Recruiting

• Conditions: Peripheral Arterial Disease; Superficial Femoral Artery Stenosis
• Interventions: Device: Plain (Uncoated) Balloon Angioplasty (PTA); Device: SELUTION SLR™ 018 DEB

• Registration Number: NCT05132361
• Lead Sponsor: MedAlliance, LLC

Brief Summary

This study aims to demonstrate the safety and efficacy of the SELUTION SLR™ 018 DEB compared to plain (uncoated) balloon angioplasty in the treatment of peripheral arterial disease (PAD) in the superficial femoral artery (SFA) and proximal popliteal artery (PPA).

Detailed Description

Prospective, multi-center, single blinded, 2:1 randomized, controlled, superiority clinical trial.

This study will enroll up to 300 randomized subjects, and up to 20 subjects in a parallel pharmacokinetic (pK) sub study, at up to 60 clinical sites in the United Stated (US), Europe (EU) and Asia. A minimum of 50% of randomized subjects will be enrolled in the US. No more than 45 subjects (15% of the total randomized cohort) can be enrolled in the randomized cohort at any single investigational site.

Randomized Cohort:

Up to 300 subjects who meet all eligibility criteria will be randomized 2:1 by permuted block method (stratified by site and adjunctive lesion preparation) to one of two treatment arms:

* Intervention - treatment with SELUTION SLR™ 018 DEB

* Control - treatment with commercially available PTA (uncoated balloon)

Pharmacokinetic (pK) Sub-study:

The pK substudy is a parallel registry consisting of up to 20 additional consecutive subjects meeting all eligibility criteria treated with the SELUTION DEB recruited at select study sites. The separate PK substudy protocol details the schedule of evaluations and blood draws to characterize the pK plasma profile of sirolimus.

Study Timeline

• Study First Submitted: 2021-11-12
• Study First Submitted QC: 2021-11-12
• Study First Posted: 2021-11-24
• Study Start: 2022-12-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-15
• Primary Completion: 2025-08-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Subject age is ≥ 18 years or minimum legal age as required by local regulations.
2. Life expectancy >1 year in opinion of investigator.
3. Documented ischemia with Rutherford classification category 2, 3 or 4.
4. Target lesion(s) in the SFA or PPA.
5. Able to walk without the assistance of a walker.
6. Subject is willing and able to provide informed consent and comply with study procedures and required follow-up evaluations.
7. Female subjects only: If female, then subjects of childbearing potential must have a negative pregnancy test ≤ 7 days before the procedure and be prepared to use effective contraception for 12 months after treatment.

Angiographic Inclusion Criteria:

1. Angiographic evidence that target lesion lies within the superficial femoral artery and/or proximal popliteal artery (P1 and P2 only).

2. Angiographic evidence that the target lesion consists of either a de novo lesion or a non-stented restenotic lesion, or a combination of both, that meets one of the following criteria:

   A. A stenosis of 70-99% with lesion length between ≥3cm and <20cm by visual estimation.

   B. A total (100%) occlusion with lesion length between ≥3cm and ≤10cm by visual estimation.

   C. A combination lesion (stenosis and total occlusion) must have a total lesion length between ≥3cm and <20cm by visual estimation with an occluded segment that is ≤10cm by visual estimation.

   D. If multiple lesions are to be treated, then only 2 lesions may be included. The total combination of lengths must be between ≥3cm and < 20cm by visual estimation, and there must be at least 5 cm of artery that is not to be treated between them.

3. Target vessel reference diameter ≥4mm and ≤7mm.

4. Patent arterial inflow (common iliac, external iliac, common femoral and profunda femoris arteries, and the proximal 2 cm of the SFA) free from significant lesion (defined as ≥50% stenosis) as confirmed on angiography.

   Note: Where required, inflow iliac arteries (common and external iliac arteries only) must be successfully treated during the index procedure. Completion angiography must confirm successful treatment of inflow disease (≤30% residual stenosis, no distal embolization, and no Grade C or greater dissection ) prior to pre-dilation and randomization of the target lesion(s). Drug-eluting devices are not allowed for treatment of the occluded inflow iliac arteries.

5. Angiographic evidence of adequate distal run off (defined as ≤50% stenosis) in one or more tibial arteries on initial angiography, and if applicable, after completion of inflow artery treatment.

Note: Treatment of outflow disease is permitted during the index procedure. Drug-eluting devices are not allowed for outflow treatment.

PK Sub-Study Inclusion Criteria:

Subjects must meet all of the main protocol inclusion criteria to participate in the PK sub-study. Subjects must also meet the following additional PK sub-study inclusion criteria:

1. Subject is willing and able to provide informed consent for the PK sub-study and comply with the PK sub-study procedures and required follow-up evaluations.

Clinical

Exclusion Criteria

1. Other surgical or endovascular procedure in the target limb that occurred within 14 days prior to index procedure or is planned for within 30 days following index procedure, with exception for diagnostic angiography.
2. Inability to tolerate dual antiplatelet therapy.
3. Known hypersensitivity or allergy to Sirolimus or other pharmacologic agents, such as contrast agent, which are required for the procedure and which cannot be adequately pre-treated.
4. Stroke or MI within 3 months of enrollment.
5. Symptom onset less than 14 days prior to index procedure (acute limb ischemia).
6. Lower limb disease in the contralateral leg that requires treatment at the index procedure, or, that is planned within 14 days prior to the index procedure or within 30 days after the index procedure.
7. Prior vascular surgery (including bypass and endarterectomy) of abdominal aorta, iliac arteries, or arteries of the index limb.
8. Non-atherosclerotic disease of the index limb (including aneurysmal disease, vasculitis, Buerger's disease)
9. Target lesion requires treatment with alternative therapies such as thrombolysis, thrombus aspiration, cutting/scoring/contoured balloon, stenting, laser, cryoplasty, intravascular lithotripsy, brachytherapy, re-entry device).
10. Subject has target lesion(s) that require treatment via pedal site.
11. Subject has target lesion(s) that require access via upper extremity arteries.
12. Hypercoagulable state or disorder present, or coagulopathy present, including platelet count less than 80,000 per microliter.
13. Chronic renal insufficiency (dialysis dependent, or serum creatinine >2.5 mg/dL within 30 days of index procedure).
14. Systemic infection (WBC > 12,000 and febrile) or known immune compromise.
15. Breast-feeding woman.
16. Currently participating in another investigational drug or device study that has not completed primary endpoint follow-up.

Angiographic Exclusion Criteria:

1. Presence of a previously placed stent in the treated artery.
2. Failure to successfully cross the target lesion.
3. Residual stenosis ≥30% after pre-dilatation.

PK Sub-Study Exclusion Criteria:

1. Subjects must meet none of the main protocol exclusion criteria (Section 6.1.2 of the main protocol) to participate in the PK sub-study. Subjects will be excluded if any of the following additional PK sub-study exclusion criteria are met:
2. Any limus family (Zotarolimus, Everolimus, Sirolimus etc.) eluting device has been placed/used in any part of the body within 3 months prior to the index procedure including non-target lesion(s) treated during the index procedure.
3. Planned intervention with any limus family (Zotarolimus, Everolimus, Sirolimus etc.) eluting device anywhere in the body within 6 months after the index procedure. Note: staged procedures >30 days after index procedure (Exclusion #20 and #22 of the main protocol) are permitted only in the main protocol, and are not permitted in this PK sub-study.
4. The subject is taking or has taken within the last 3 months any limus family medication(s) for any reason.
5. Subjects who are taking strong CYP3A4 Inhibitors within 14 days before the index procedure or plan to take the strong inhibitors during the study period. Strong inhibitors include: cobicistat; ritonavir; indinavir and ritonavir; itraconazole; ketoconazole; lopinavir and ritonavir; paritaprevir and ritonavir and ombitasvir (and/or dasabuvir); posaconazole; saquinavir and ritonavir; tipranavir and ritonavir; elvitegravir and ritonavir; telithromycin; voriconazole; ceritinib; clarithromycin; idealalisib; nefazodone; nelfinavir.
6. Subjects who are taking strong CYP3A4 Inducers within 14 days before the index procedure or plan to take the strong inducers during the study period. Strong inducers include apalutamide; carbamazepine; enzalutamide; ivosidenib; lumacaftor and ivacaftor; mitotane; phenytoin; rifampin; St. John's wort.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plain (Uncoated) Balloon Angioplasty (PTA)	Plain (Uncoated) Balloon Angioplasty (PTA)	Opening artery only by dilatation with an temporary inserted and inflated balloon.
SELUTION SLR™ 018 DEB	SELUTION SLR™ 018 DEB	Treatment with Selution SLR drug eluting balloon to apply long term (\>90 days) local treatment with sirolimus

Primary Outcome Measures

Name	Time	Method
Primary Safety Endpoint	30 days or 12 months	The primary safety endpoint is the freedom from ANY of the following adverse events: * All-cause perioperative death (POD) \[evaluated at 30 days\] OR; * Target limb major (above-the-ankle) amputation \[evaluated at 12 months\] OR; * Clinically driven target lesion revascularization (CD-TLR) \[evaluated at 12 months\]
PK Sub-Study Primary Endpoint MRT(last)	6 months	PK parameters of Mean Residence Time(last).
Primary Efficacy Endpoint	12 months	Primary patency of the target lesion defined as freedom from ANY of the following adverse events: * Clinically driven target lesion revascularization (CD-TLR, defined as re-intervention of target lesion(s) due to recurrent, persistent, or worsening symptoms and angiographic restenosis (≥ 50% diameter stenosis) of target lesion by ACL measurement) OR; * Restenosis as determined by core lab adjudicated duplex ultrasound peak systolic velocity ratio of \>2.4 or occlusion of the target lesion.
PK Sub-Study Primary Endpoint: T(max)	6 months	PK parameters of T(max).
PK Sub-Study Primary Endpoint: AUC(last)	6 months	PK parameters of AUC(last).
PK Sub-Study Primary Endpoint: C(max)	6 months	PK parameters of C(max).

Secondary Outcome Measures

Name	Time	Method
Powered Secondary Endpoints	12 months	If both primary endpoints are met, the following endpoint will be tested for superiority in a sequential manner: • Clinically driven target lesion revascularization (CD-TLR)
Procedural (technical) success	Immediately following the procedure	A secondary performance endpoint defined as device success and residual diameter stenosis ≤ 30% on completion angiography by core lab assessment.
Clinically driven Target Vessel Revascularization (TVR)	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as re-intervention of target vessel due to recurrent/persistent/worsening symptoms and the angiographic finding of ≥ 50% restenosis of target vessel by ACL measurement.
Device success	Immediately following the procedure	A secondary performance endpoint defined as successful delivery, balloon inflation, deflation, and retrieval of the intact investigational device.
Clinical success	Discharge defined as immediately prior to hospital discharge from the index procedure or within 7 days, whichever occurs first	A secondary performance endpoint defined as procedural success without procedural complications (death, above-ankle target limb amputation, thrombosis of the target lesion or TLR) prior to discharge.
Freedom from CD-TLR and binary restenosis	1, 3, 6, 12, 24, 36 months	A secondary efficacy endpoint defined as freedom from Clinically driven target lesion revascularization and binary restenosis as determined by the duplex ultrasound core laboratory (DCL).
Any TLR	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as any re-intervention of target lesion(s).
Ankle brachial index (ABI)	12 and 24 months	A secondary efficacy endpoint defined as change in ankle brachial index (ABI) from baseline.
PK Sub-Study Secondary Endpoint: half-life	6 months	If calculations are valid, additional PK parameter of half-life.
Secondary Safety Endpoints	1, 6, and 12 months, and 2-5 years	* Major adverse limb events (MALE).; * Major cardiovascular events, myocardial infarction (MI), and stroke.; * All-cause mortality.
Primary sustained clinical improvement	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as freedom from target limb major amputation and CD-TLR AND increase in Rutherford category from baseline.
Major amputation	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as above-the-ankle amputation of the target limb.
CD-TLR	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as re-intervention of target lesion(s) due to recurrent/persistent/worsening symptoms and the angiographic finding of ≥ 50% restenosis of target lesion by ACL measurement.
Target lesion thrombosis	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint assessed by angiographic or DUS core laboratory adjudication.
Walking capacity	1, 6, 12, 24 and 36 months	A secondary efficacy endpoint defined as change in Walking capacity assessed by Walking Impairment Questionnaire (WIQ) from baseline.
Secondary Quality of life and health economic assessments (1)	12 months	• Change in EQ-5D score from baseline. OBS.: Following EuroQol terminology: Scores are anchored at 1 (full health) and 0 (a state as bad as being dead) as required by their use in economic evaluation. Values less than 0 represent health states regarded as worse than a state that is as bad as being dead.
Secondary sustained clinical improvement	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as freedom from target limb major amputation AND increase in Rutherford category from baseline.; * Major amputation, defined as above-the-ankle amputation of the target limb.; * Amputation-free survival, defined as freedom from all-cause mortality and major amputation.
Amputation-free survival	1, 6, and 12 months, and 2-5 years	A secondary efficacy endpoint defined as freedom from all-cause mortality and major amputation.
Primary assisted patency	12 and 24 months	A secondary efficacy endpoint defined as freedom from target lesion occlusion by duplex ultrasound core laboratory \[DCL\] adjudication), irrespective of interventions for stenoses.
Secondary patency	12 and 24 months	A secondary efficacy endpoint defined as freedom from permanent occlusion (occlusion at the last follow-up imaging) as determined by the DCL.; * Freedom from CD-TLR and binary restenosis as determined by the DCL \[at 1, 3, 6, 12, 24, 36 months\].; * Any TLR, defined as any re-intervention of target lesion(s) 1, 6, and 12 months, and 2-5 years
Rutherford category	1, 6, 12, 24 and 36 months	A secondary efficacy endpoint defined as change in Rutherford category from baseline.
PK Sub-Study Secondary Endpoint: Vss	6 months	If calculations are valid, additional PK parameter of Vss.
Secondary Imaging endpoints (DCL adjudicated):	12 and 24 months	* Primary duplex-defined binary restenosis - Peak Systolic Velocity Ratio (PSVR)\>2.4.; * Alternate duplex-defined binary restenosis - Peak Systolic Velocity Ratio (PSVR)\>3.4.
Secondary Quality of life and health economic assessments (2)	12 months	• Days of target lesion-related hospitalization at 12 months.
PK Sub-Study Secondary Endpoint: AUC(inf)	6 months	If calculations are valid, additional PK parameter of AUC(inf).
PK Sub-Study Secondary Endpoint: Cl	6 months	If calculations are valid, additional PK parameter of Cl.
PK Sub-Study Secondary Endpoint: Vz	6 months	If calculations are valid, additional PK parameter of Vz.
PK Sub-Study Secondary Endpoint: C(max)	6 months	Dose normalized C(max) will be considered if appropriate.
PK Sub-Study Secondary Endpoint: AUC	6 months	Dose normalized AUC will be considered if appropriate.

Trial Locations

Locations (42)

St. Bernards Medical Center; 🇺🇸 Jonesboro, Arkansas, United States

Arkansas Heart Hospital; 🇺🇸 Little Rock, Arkansas, United States

Mission Cardiovascular Research Institute; 🇺🇸 Fremont, California, United States

St. Helena Hospital; 🇺🇸 Saint Helena, California, United States

ClinRé; 🇺🇸 Thornton, Colorado, United States

Vascular Care Group; 🇺🇸 Darien, Connecticut, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Manatee Memorial Hospital; 🇺🇸 Bradenton, Florida, United States

The Cardiac and Vascular Institute Research Foundation; 🇺🇸 Gainesville, Florida, United States

Palm Vascular Centers; 🇺🇸 Miami Beach, Florida, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Cardiovascular Consultants of South Georgia; 🇺🇸 Thomasville, Georgia, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Memorial Healthcare System; 🇺🇸 Hollywood, Florida, United States

First Coast Cardiovascular Institute; 🇺🇸 Jacksonville, Florida, United States

Guardian Research Organization, LLC; 🇺🇸 Winter Park, Florida, United States

Heart Care Centers Research Foundation; 🇺🇸 Palos Park, Illinois, United States

Advocate Lutheran General Hospital; 🇺🇸 Park Ridge, Illinois, United States

Cardiovascular Institute of the South; 🇺🇸 Gray, Louisiana, United States

MedStar Health Research Institute; 🇺🇸 Hyattsville, Maryland, United States

Mercy Hospital; 🇺🇸 Saint Louis, Missouri, United States

Holy Name Medical Center; 🇺🇸 Teaneck, New Jersey, United States

James J. Peters VA Medical Center; 🇺🇸 Bronx, New York, United States

Mount Sinai; 🇺🇸 New York, New York, United States

NC Heart and Vascular Research, LLC; 🇺🇸 Raleigh, North Carolina, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

OhioHealth Riverside Hospital; 🇺🇸 Columbus, Ohio, United States

Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States

Tennessee Center for Clinical Trials; 🇺🇸 Tullahoma, Tennessee, United States

El Paso Cardiology; 🇺🇸 El Paso, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Heart Hospital Baylor Plano; 🇺🇸 Plano, Texas, United States

Texas Cardiac and Vascular Institute San Antonio; 🇺🇸 San Antonio, Texas, United States

Universitätsklinikum Graz; 🇦🇹 Graz, Austria

Alexianer Klinikum Hochsauerland; 🇩🇪 Arnsberg, Germany

Universitäts-Herzzentrum Freiburg - Bad Krozingen; 🇩🇪 Bad Krozingen, Germany

Krankenhaus Buchholz; 🇩🇪 Buchholz, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

RoMed Klinikum Rosenheim; 🇩🇪 Rosenheim, Germany

University Clinic Tübingen; 🇩🇪 Tübingen, Germany

Queen Mary Hospital; 🇭🇰 Hong Kong, Pok Fu Lam, Hong Kong

The Chinese University of Hong Kong; 🇭🇰 Sha Tin, Hong Kong