Sirolimus- vs. Paclitaxel-Drug Coated Ballons in Patients With Peripheral Artery Disease

Study Overview
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Brief Summary
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This study is a prospective, interventional, multi-center 1:1 randomized non-inferiority trial. The trial evaluates the safety and efficacy of the Magic Touch PTA sirolimus drug-coated balloon in comparison to the treatment with PTX drug-coated balloon (control device) in patients with femoropopliteal artery disease.

Detailed Description
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Percutaneous transluminal angioplasty (PTA), in which a balloon is advanced and inflated in the obstructed artery for several seconds to minutes, has become the standard endovascular treatment for peripheral arteries. The long-term success of bare balloon PTA in the fem-oropopliteal segment is hampered by the occurrence of restenosis, which can be reduced by local antiproliferative drug delivery via the PTA balloon catheter. The rationale of this study is based on the hypothesis that the usage of the Sirolimus-coated Magic Touch Sirolimus DCB is at least equal (non-inferior) with regards to efficacy and safety in comparison with a clinically well-established PTX coated balloon. The objective of this prospective, randomized, multi-center, post-market study is to compare the Magic Touch Sirolimus DCB with Paclitaxel-coated DCB for treatment of high grade ste-notic or occluded lesions in SFA and / or P1 segment of the popliteal artery (PA) in PAD pa-tients.

Official Title
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Head-to-Head Comparison of SIROlimus Versus Paclitaxel Drug-Eluting BallooN Angioplasty in the Femoropopliteal Artery

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Combination Product: Percutaneous Transluminal Angioplasty (PTA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject age ≥ 18 Subject has been informed on the nature of the study, the duration of the study, agrees to attend follow-up visits, agrees to complete the required testing, agrees to participate, and has signed an informed consent form. Rutherford category 2-4 according to the investigator's subjective evaluation Subject has a de novo or re-stenosed lesion with ≥ 70 % stenosis documented angiographically Target lesion length is ≥ 2 cm and ≤ 20 cm by visual estimate of the treating physician Multiple lesions with max. 3 cm healthy vessel segment in between lesions can be considered at the discretion of the operator as one lesion. Total lesion length should not exceed 20 cm Reference vessel diameter (RVD) ≥ 4 mm and ≤ 6.5 mm by visual estimation Patency of P2 and P3 segment of the popliteal artery and at least one (1) infrapopliteal artery to the ankle (< 50 % diameter stenosis) in continuity with the femoropopliteal artery Patency of ipsilateral iliac artery (≤ 30% diameter stenosis). Iliac artery stenosis > 30 % may be treated during the index procedure to ensure sufficient inflow. A guidewire has successfully traversed the target treatment segment intraluminal Vascular disease in the opposite leg that requires treatment at the time point of index procedure is allowed, but has to be treated according to randomization or with POBA. A patient can only be enrolled and randomized once with only one target lesion in the SIRONA trial. Please note that only the lesion in one limb can be treated as target lesion for index procedure. Exclusion Criteria: Failure to successfully cross the target lesion or subintimal target lesion guidewire crossing Flow-limiting dissection after pre-dilatation Angiographic evidence of severe calcification of the target vessel (contiguous calcification on both sides of the vessel) Presence of fresh thrombus in the target lesion Presence of aneurysm in the target vessel/s Prior vascular surgery (including atherectomy, bypass surgery) of the target limb Prior stent in the target lesion Stroke or heart attack within 3 months prior to enrollment Any vascular surgical procedure or intervention performed in the target limb within 30 days prior to or planned within 30 days post index procedure Any vascular treatment with PTX or sirolimus-coated devices 60 days prior to index procedure Target lesion requires treatment with alternative therapies such as primary stenting, laser, lithotripsy, thrombectomy, atherectomy, cryoplasty, brachytherapy, re-entry devices Enrolled in another investigational drug, device or biologic study Life expectancy of less than one year in the investigator's opinion Known allergies or sensitivity to heparin, aspirin, other anticoagulant/ antiplatelet therapies, sirolimus, paclitaxel or contrast media that cannot be adequately pre-treated prior to index procedure Significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy Receiving dialysis or immunosuppressant therapy Pregnant or lactating females History of major amputation in the same limb as the target lesion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1-randomization, parallel design, stratified by Center.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sirolomus DCB group<br>Intervention with Sirolimus-coated balloon catheter | Combination Product: Percutaneous Transluminal Angioplasty (PTA)<br>* PTA with an drug-coated balloon catheter (DCB) in the femoropopliteal artery<br>|
| Active Comparator: Paclitaxel DCB group<br>Intervention with Paclitaxel-coated balloon catheter | Combination Product: Percutaneous Transluminal Angioplasty (PTA)<br>* PTA with an drug-coated balloon catheter (DCB) in the femoropopliteal artery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patency rate (Absence of clinically driven target lesion revascularization) | patency rate after one year defined as absence of clinically driven target lesion revascularization (TLR) due to symptoms and drop of ABI of ≥ 20% or > 0.15 when compared to post-procedure or restenosis with PVR > 2.4 evaluated by duplex ultrasound | one year after study procedure (PTA with medical product under investigation or comparator) | 
| Safety outcome | Composite of freedom from device and procedure-related death through 12 months post procedure as well as freedom from both target limb major amputation and clinically-driven target vessel vessel revasculariza-tion | through 12 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TLR rate | ocurrence of Target lesion revascularization (TLR) at certain time Points | 1, 6, 12, 24, 36, 48 and 60 months after study procedure | 
| Rutherford classification | Sustained clinical improvement: an improvement shift in the Rutherford classification of one class in amputation and TVR free surviving patients | at 12 months after study procedure | 
| Walking capacity assessment 1 | patient-self-assessment of walking distance | at 1, 6, 12, 24, 36, 48 and 60 months after study procedure | 
| Walking capacity assessment 2 | 6-minute Walking test (6MWT) | at 6, 12, 24, 48 months after study procedure | 
| Walking capacity assessment 3 | Treadmill test (optional) | at 6, 12, 24, 48 months after study procedure | 
| Walking capacity assessment 4 | Walking Impairment Questionnaire (WIQ); 20 questions (scale 0 to 4); best score 0, worst score 80 | at 6, 12, 24, 48 months after study procedure | 
| Duplex Ultrasound | Duplex-defined binary restenosis (PSVR >2.4) of the target lesion | post-procedure and at 6, 12, 24 and 48 months or at any time of re-intervention | 
| ABI | Ankle brachial index (ABI) | at discharge, 6, 12, 24 and 48 months | 
| Qualilty of Life Assessment | Quality of life assessment (QoL) by EQ5D-3L questionnaire; 5 questions (scale 1 to 5), best score 5, worst score 25 | at 1 month, 6, 12, 24, 36, 48 and 60 months | 
| Secondary Safety: freedom from all cause death, target limb major amputation and clinically-driven target vessel revascularization | Composite of freedom from all cause death through 60 months post procedure as well as freedom from both target limb major amputation and clinically-driven target vessel revascularization | trough 60 months after study procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Artery Disease, Sirolimus, Paclitaxel, Drug-Coated Balloon, Percuteanous Transaluminal Angioplasty, PPA, SFA, MagicTouch PTA