Clinical trial NCT05132361: SELUTION4SFA Trial
Official title: A Prospective Randomized Multicenter Single Blinded Study to Assess the Safety and Efficacy of the SELUTION SLR™ 018 Drug Eluting Balloon in the Treatment of Subjects With Femoropopliteal Artery Lesions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Arterial Disease
Superficial Femoral Artery Stenosis
Lead sponsor: M.A. Med Alliance S.A.
Sponsor class: INDUSTRY
Collaborators: name: NAMSA
name: Cordis Corporation
First posted: 2021-11-24
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Clinical 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.

Primary outcomes:
measure: Primary Efficacy Endpoint
timeFrame: 12 months
measure: Primary Safety Endpoint
timeFrame: 30 days or 12 months
measure: PK Sub-Study Primary Endpoint: C(max)
timeFrame: 6 months
measure: PK Sub-Study Primary Endpoint: T(max)
timeFrame: 6 months
measure: PK Sub-Study Primary Endpoint: AUC(last)
timeFrame: 6 months
measure: PK Sub-Study Primary Endpoint MRT(last)
timeFrame: 6 months
Secondary outcomes:
measure: Powered Secondary Endpoints
timeFrame: 12 months
measure: Device success
timeFrame: Immediately following the procedure
measure: Procedural (technical) success
timeFrame: Immediately following the procedure
measure: Clinical success
timeFrame: Discharge defined as immediately prior to hospital discharge from the index procedure or within 7 days, whichever occurs first
measure: Secondary Safety Endpoints
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Primary sustained clinical improvement
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Secondary sustained clinical improvement
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Major amputation
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Amputation-free survival
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Primary assisted patency
timeFrame: 12 and 24 months
measure: Secondary patency
timeFrame: 12 and 24 months
measure: Freedom from CD-TLR and binary restenosis
timeFrame: 1, 3, 6, 12, 24, 36 months
measure: Any TLR
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: CD-TLR
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Clinically driven Target Vessel Revascularization (TVR)
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Target lesion thrombosis
timeFrame: 1, 6, and 12 months, and 2-5 years
measure: Rutherford category
timeFrame: 1, 6, 12, 24 and 36 months
measure: Ankle brachial index (ABI)
timeFrame: 12 and 24 months
measure: Walking capacity
timeFrame: 1, 6, 12, 24 and 36 months
measure: Secondary Imaging endpoints (DCL adjudicated):
timeFrame: 12 and 24 months
measure: Secondary Quality of life and health economic assessments (1)
timeFrame: 12 months
measure: Secondary Quality of life and health economic assessments (2)
timeFrame: 12 months
measure: PK Sub-Study Secondary Endpoint: AUC(inf)
timeFrame: 6 months
measure: PK Sub-Study Secondary Endpoint: Cl
timeFrame: 6 months
measure: PK Sub-Study Secondary Endpoint: Vz
timeFrame: 6 months
measure: PK Sub-Study Secondary Endpoint: Vss
timeFrame: 6 months
measure: PK Sub-Study Secondary Endpoint: half-life
timeFrame: 6 months
measure: PK Sub-Study Secondary Endpoint: C(max)
timeFrame: 6 months
measure: PK Sub-Study Secondary Endpoint: AUC
timeFrame: 6 months
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: St. Bernards Medical Center
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Fremont
country: United States
facility: Mission Cardiovascular Research Institute
state: California
city: Saint Helena
country: United States
facility: St. Helena Hospital
state: California
city: Thornton
country: United States
facility: ClinRé
state: Colorado
city: Darien
country: United States
facility: Vascular Care Group
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Bradenton
country: United States
facility: Manatee Memorial Hospital
state: Florida
city: Gainesville
country: United States
facility: The Cardiac and Vascular Institute Research Foundation
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Miami Beach
country: United States
facility: Palm Vascular Centers
state: Florida
city: Winter Park
country: United States
facility: Guardian Research Organization, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Thomasville
country: United States
facility: Cardiovascular Consultants of South Georgia
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Palos Park
country: United States
facility: Heart Care Centers Research Foundation
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Gray
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Hyattsville
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Saint Louis
country: United States
facility: Mercy Hospital
state: Missouri
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Bronx
country: United States
facility: James J. Peters VA Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Raleigh
country: United States
facility: NC Heart and Vascular Research, LLC
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Hospital
state: Ohio
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: El Paso
country: United States
facility: El Paso Cardiology
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Plano
country: United States
facility: Heart Hospital Baylor Plano
state: Texas
city: San Antonio
country: United States
facility: Texas Cardiac and Vascular Institute San Antonio
state: Texas
city: Graz
country: Austria
facility: Universitätsklinikum Graz
city: Arnsberg
country: Germany
facility: Alexianer Klinikum Hochsauerland
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg - Bad Krozingen
city: Buchholz
country: Germany
facility: Krankenhaus Buchholz
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
city: Tübingen
country: Germany
facility: University Clinic Tübingen
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
state: Pok Fu Lam
city: Sha Tin
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
References: