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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral Artery Disease
• Intervention / Treatment: Combination product: Percutaneous Transluminal Angioplasty (PTA)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 478
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medizinische Universität Graz, Klinische Abteilung für Angiologie
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Wörthersee, Institut für Diagnostische und Interventionelle Radiologie
  • Vienna, Austria, A-1090
    • Medical University Vienna, Universitätsklinik für Innere Medizin II, Klinische Abteilung für Angiologie
  • Wien, Austria, 1090
    • Universitätsklinik für Radiologie und Nuklearmedizin, Klinische Abteilung für Kardiovaskuläre und Interventionelle Radiologie
  • Wien, Austria, 1140
    • Hanusch-Krankenhaus
• Germany
  • Bad Krozingen, Germany, 79189
    • University Heart Center Freiburg-Bad Krozingen
  • Berlin, Germany, 12203
    • Charité Universitätsmedizin, Klinik für Radiologie
  • Bruchsal, Germany, 76646
    • Fürst-Stirum-Klinik Bruchsal, Klinik für Kardiologie, Angiologie, Diabetologie, Neurologie und Intensivmedizin
  • Dresden, Germany, 01307
    • Universitätsklinikum Dresden, Institut und Poliklinik für Diagnostische und Interventionelle Radiologie
  • Essen, Germany, 45147
    • Universitätsklinikum Essen, Westdeutsches Herz- und Gefäßzentrum Essen, Klinik für Kardiologie und Angiologie
  • Flensburg, Germany, 24939
    • DIAKO Krankenhaus gGmbH, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie
  • Halle (Saale), Germany, 06120
    • Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Radiologie
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg, Medizinische Klinik III, Kardiologie, Angiologie und Pneumologie
  • Immenstadt Im Allgäu, Germany, 87509
    • Klinikverbund Allgäu gGmbH, Herz- und Gefäßzentrum Oberallgäu Kempten, Klinik Immenstadt
  • Jena, Germany, 07747
    • University Hospital Jena
  • Krefeld, Germany, 47805
    • Helios Klinikum Krefeld, Institut für Diagnostische und Interventionelle Radiologie
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig, Klinik und Poliklinik für Angiologie
  • Mainz, Germany, 55131
    • Marienhaus Klinikum Mainz, Klinik für Diagnostische und Interventionelle Radiologie
  • München, Germany, 80331
    • Gefäßpraxis im Tal
  • Münster, Germany, 48145
    • St. Franziskus-Hospital GmbH, Klinik für Gefäßchirurgie
  • Münster, Germany, 48149
    • Universitätsklinikum Münster, Klinik für Kardiologie I, Koronare Herzkrankheit, Herzinsuffizienz und Angiologie
  • Radebeul, Germany, 01445
    • Elblandklinikum Radebeul, Gefäßzentrum
  • Rendsburg, Germany, 24768
    • Schön Klinik Rendsburg, Institut für Diagnostische und Interventionelle Radiologie/Neuroradiologie
  • Rosenheim, Germany, 83022
    • RoMed Klinikum Rosenheim, Diagnostische und Interventionelle Radiologie
  • Sonneberg, Germany, 96515
    • MEDINOS-Kliniken Sonneberg, Gefäßzentrum
  • Torgau, Germany, 04860
    • Kreiskrankenhaus Torgau, Abt. Innere Medizin / Angiologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Sirolomus DCB group; Intervention with Sirolimus-coated balloon catheter	Combination product: Percutaneous Transluminal Angioplasty (PTA); PTA with an drug-coated balloon catheter (DCB) in the femoropopliteal artery
Active Comparator: Paclitaxel DCB group; Intervention with Paclitaxel-coated balloon catheter	Combination product: Percutaneous Transluminal Angioplasty (PTA); PTA with an drug-coated balloon catheter (DCB) in the femoropopliteal artery

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: Concept Medical Inc.; Center for Clinical Studies, Jena University Hospital; CoreLab Black Forest; Vascuscience
• Investigators: Study Director: Ulf Teichgraeber, Prof. Dr., University Hospital Jena, Institute of Radiology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Drug-Coated Balloon; Peripheral Artery Disease; Sirolimus; Paclitaxel; SFA; PPA; Percuteanous Transaluminal Angioplasty; MagicTouch PTA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease
• Other Study ID Numbers: ZKSJ0127; DRKS00022452 (Other Identifier: German Registry for Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No