Vascular Effects Through Sirolimus vs. Paclitaxel DCB Implantation

Scientific Proposal to Substantiate Vascular Effects Through Sirolimus vs. Paclitaxel DCB Implantation

Endovascular treatment of symptomatic atherosclerotic peripheral artery disease (PAD) is recommended as the primary revascularization strategy. Percutaneous transluminal angioplasty (PTA) of the superficial femoral artery has a high initial success rate, but restenosis and dissections frequently occur.The influence of the novel devices with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance can be measured by FMD (flow-mediated dilation), arterial stiffness indices and vascular strain analysis. The aim of this ITT is to determine the potential improvement and impact of the SELUTION SLR in the infrainguinal arteries on local vascular function.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease; Drug Eluting Balloon; Infrainguinal Peripheral Arterial Disease; Flow-mediated Dilation
• Intervention / Treatment: Device: SELUTION SLR DCB; Device: Paclitaxel DCB

Detailed Description

Endovascular treatment of symptomatic atherosclerotic peripheral artery disease (PAD) is recommended as the primary revascularization strategy. Percutaneous transluminal angioplasty (PTA) of the superficial femoral artery has a high initial success rate, but restenosis and dissections frequently occur. While restoration of tissue perfusion is achieved, these interventional strategies affect vascular function, perpetuating dysfunctional vascular homeostasis. Vascular and endothelial dysfunction per se is the pathophysiologic principle involved in the initiation and progression of atherosclerosis and has been correlated to higher incidences of cardiac events such as myocardial infarction or the need for interventions. PTA and DCB treatment alter the endothelial homeostasis but the impact and detailed mechanisms are incompletely understood. The influence of the novel devices with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance can be measured by FMD (flow-mediated dilation), arterial stiffness indices and vascular strain analysis.

The aim of this ITT is to determine the potential improvement and impact of the SELUTION SLR in the infrainguinal arteries on local vascular function.

Device to be used are SELUTION SLR™ (Sustained Limus Release) drug eluting balloon (n = 35) vs. Active comparator, Paclitaxel eluting balloon (Medtronic InPact, n = 35)

The analysis of the primary end point will be performed on an intention-to-treat basis.

Subgroup analyses will be performed according to PAD classification etiology and based on stent length.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christos Rammos, Professor; Phone Number: 0201-723-84808; Email: christos.rammos@uk-essen.de
• Study Contact Backup: Name: Tienush Rassaf, Univ.-Prof.; Phone Number: 0201-723-4801; Email: tienush.rassaf@uk-essen.de

Study Locations

• Germany
  • NRW
    • Essen, NRW, Germany, 45147
      • Recruiting
      • University of Essen, Clinic of Cardiology and Angiology
      • Contact: Christos Rammos, Prof.; Phone Number: +4920172384808; Email: christos.rammos@uk-essen.de
      • Contact: Tienush Rassaf, Univ.-Prof.; Phone Number: +492017234801; Email: tienush.rassaf@uk-essen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Peripheral artery disease
• Target lesions 3 cm distal to the CFA-bifurcation including SFA and PA lesions
• Clinical diagnosis of chronic, symptomatic lower limb ischemia as defined by Rutherford 2, 3, 4 and 5
• Planed peripheral intervention TASC A-D
• Subject must be between 18 and 85 years old
• Female of childbearing potential must have a negative pregnancy test within 10 days prior to index procedure and utilize reliable birth control until completion of the 12-month angiographic evaluation
• Vessel diameter ≥4.0 mm and ≤7.0 mm
• Willing to comply with the specified follow-up evaluation
• Written informed consent prior to any study procedures
• Pretreatment with an adequately sized balloon

Exclusion Criteria:

• Bifurcational lesions of the CFA and lesions including the first 3 cm of the SFA, due to technical aspects of FMD measurement
• Instent-Restenosis
• Thrombolysis within 72 hours prior to the index procedure
• Aneurysm formations in the femoral artery or popliteal artery
• Concomitant hepatic insufficiency, deep venous thrombus, coagulation disorder or receiving immunosuppressant therapy
• Unstable angina pectoris at the time of the enrollment
• Recent myocardial infarction or stroke < 30 days prior to the index procedure
• Life expectancy less than 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SELUTION SLR DCB; Sustained Limus Release drug eluting balloon	Device: SELUTION SLR DCB; Sirolimus DCB
Active Comparator: Paclitaxel eluting balloon; Conventional: Medtronic INpact	Device: Paclitaxel DCB; Paclitaxel DCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of flow-mediated vasodilation (FMD) of the nonstenotic segment of the proximal SFA after procedure	FMD represents the percent diameter gain as calculated based on preischemia and postischemia diameter measurements of the femoral artery	1 month
Change of flow-mediated vasodilation (FMD) of the nonstenotic segment of the proximal SFA after procedure	FMD represents the percent diameter gain as calculated based on preischemia and postischemia diameter measurements of the femoral artery	6 months
Change of flow-mediated vasodilation (FMD) of the nonstenotic segment of the proximal SFA after procedure	FMD represents the percent diameter gain as calculated based on preischemia and postischemia diameter measurements of the femoral artery	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in pulse wave velocity (PWV)	Changes in cardiovascular function measured by pulse wave velocity in m/s	Baseline, followed at 1, 6 and 12 months
Changes in augmentation index	Changes in cardiovascular function measured by augmentation index in %	Baseline, followed at 1, 6 and 12 months
Changes in vascular strain	Changes in cardiovascular function measured by vascular strain in %	Baseline, followed at 1, 6 and 12 months
Changes in peripheral perfusion determined by ABI (ankle brachial index)	ABI measurements are conducted using a Doppler probe on tibial and anterior artery locations. The highest value will be used for calculation and divided by the highest systolic brachial Doppler pressure	Baseline, followed at 1, 6 and 12 months
Primary patency (PP) of target lesion	Primary patency determined by PVR measurement with ultrasound	Baseline, followed at 1, 6 and 12 months
Changes in clinical symptoms	Clinical symptoms of patients determined by Walking impairment questionaire (WIQ)	Baseline, followed at 1, 6 and 12 months
Changes in six-minute walk test	Six-minute walk test determined by pain-free walking distance in m	Baseline, followed at 1, 6 and 12 months
Procedural complications	Any procedural complications	Baseline, followed at 1, 6 and 12 months
Freedom from Target Lesion Revascularization	Freedom from Target Lesion Revascularization (FTLR)	Baseline, followed at 1, 6 and 12 months
MALE	Any unplanned vascular event and minor or major amputations	Baseline, followed at 1, 6 and 12 months
Changes of inflammatory profile measured by hs-CRP in mg/dl	Blood samples are collected at the below mentioned time points	Baseline, followed at 1, 6 and 12 months
Changes of inflammatory profile measured by oxLDL in µg/l	Blood samples are collected at the below mentioned time points	Baseline, followed at 1, 6 and 12 months
Changes of inflammatory profile measured by Interleukin-6 in pg/ml	Blood samples are collected at the below mentioned time points	Baseline, followed at 1, 6 and 12 months

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Investigators: Principal Investigator: Christos Rammos, Professor, University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2022
• Primary Completion (Estimated): April 6, 2024
• Study Completion (Estimated): April 6, 2024

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Percutaneous transluminal angioplasty; Paclitaxel eluting ballon; Sirolimus eluting ballon
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: The Limus FLOW Study

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