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

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.

• Percutaneous Transluminal Angioplasty (PTA) (Combination product): PTA with an drug-coated balloon catheter (DCB) in the femoropopliteal artery

Primary outcomes

• Patency rate (Absence of clinically driven target lesion revascularization) [one year after study procedure (PTA with medical product under investigation or comparator)]: 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
• Safety outcome [through 12 months post-procedure]: 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

Secondary outcomes

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

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Subject age ≥ 18
2. 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.
3. Rutherford category 2-4 according to the investigator's subjective evaluation
4. Subject has a de novo or re-stenosed lesion with ≥ 70 % stenosis documented angiographically
5. Target lesion length is ≥ 2 cm and ≤ 20 cm by visual estimate of the treating physician
6. 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
7. Reference vessel diameter (RVD) ≥ 4 mm and ≤ 6.5 mm by visual estimation
8. 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
9. Patency of ipsilateral iliac artery (≤ 30% diameter stenosis). Iliac artery stenosis > 30 % may be treated during the index procedure to ensure sufficient inflow.
10. A guidewire has successfully traversed the target treatment segment intraluminal
11. 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.
12. 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:

1. Failure to successfully cross the target lesion or subintimal target lesion guidewire crossing
2. Flow-limiting dissection after pre-dilatation
3. Angiographic evidence of severe calcification of the target vessel (contiguous calcification on both sides of the vessel)
4. Presence of fresh thrombus in the target lesion
5. Presence of aneurysm in the target vessel/s
6. Prior vascular surgery (including atherectomy, bypass surgery) of the target limb
7. Prior stent in the target lesion
8. Stroke or heart attack within 3 months prior to enrollment
9. Any vascular surgical procedure or intervention performed in the target limb within 30 days prior to or planned within 30 days post index procedure
10. Any vascular treatment with PTX or sirolimus-coated devices 60 days prior to index procedure
11. Target lesion requires treatment with alternative therapies such as primary stenting, laser, lithotripsy, thrombectomy, atherectomy, cryoplasty, brachytherapy, re-entry devices
12. Enrolled in another investigational drug, device or biologic study
13. Life expectancy of less than one year in the investigator's opinion
14. 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
15. Significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy
16. Receiving dialysis or immunosuppressant therapy
17. Pregnant or lactating females
18. History of major amputation in the same limb as the target lesion

• Teichgraber U, Ingwersen M, Platzer S, Lehmann T, Zeller T, Aschenbach R, Scheinert D. Head-to-head comparison of sirolimus- versus paclitaxel-coated balloon angioplasty in the femoropopliteal artery: study protocol for the randomized controlled SIRONA trial. Trials. 2021 Sep 28;22(1):665. doi: 10.1186/s13063-021-05631-9. PMID 34583746
• Results publication: Teichgraber U, Ingwersen M, Lehmann T, Platzer S, Kunstmann I, Steiner S, Schmidt A, Wittig T, Zeller T, Thieme M, Krankenberg H, Werner M, Brodmann M, Malyar N, Muller-Hulsbeck S, de Paoli L, Schlager O, Austermann M, Tepe G, Erbel C, Ito W, Wassmer R, Maiwald L, Aschenbach R, Wissgott C, Andrassy M, Wolf F, Beschorner U, Pech M, Katsanos K, Scheinert D. Subgroup variations in effectiveness of femoropopliteal sirolimus versus paclitaxel-coated balloon angioplasty: post hoc results of the randomised SIRONA trial. CVIR Endovasc. 2026 Aug 11;9(1):96. doi: 10.1186/s42155-026-00743-2. PMID 42576093

• Ulf Teichgraeber, Prof. Dr., Study director, University Hospital Jena, Institute of Radiology