Clinical trial NCT04772300: Trial to Assess the Safety and Efficacy of Sirolimus-Coated Balloon vs. Uncoated Standard Angioplasty for the Treatment of Below-the-knee Peripheral Arterial Disease
Official title: Prospective Multi-Center Randomized Controlled Trial to Evaluate the Safety and Efficacy of SiroLIMus Drug Coated Balloon Versus Non-coated Standard Angioplasty for the Treatment of Infrapopliteal Occlusions in Patients With PEripheral Arterial DiSease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Artery Disease
Keywords: Peripheral Artery Disease
Sirolimus
Drug-Coated Balloon
Percuteanous Transluminal Angioplasty
MagicTouch
Below-the-knee
BTK
Drug-Coated Ballon
plain old angioplasty
POBA
Randomized-Controlled Trial
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
Collaborators: name: Concept Medical Inc.
name: Vascuscience
name: CoreLab Black Forest
name: Center for Clinical Studies, University Hospital Jena
First posted: 2021-02-26
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1-randomization, parallel design, stratified by center.
Primary purpose: TREATMENT

Brief summary: This study is a prospective, interventional, multicenter 1:1 randomized trial.

The trial evaluates the safety and efficacy of the Magic Touch PTA sirolimus drug-coated balloon in comparison to the treatment with POBA (control device) in patients with advanced infrapopliteal artery disease.

Detailed description: The purpose of this study is to assess whether efficacy of the MagicTouch® Sirolimus Coated PTA Balloon Catheter (SRL-DCB) is superior and whether safety is non-inferior to Plain Old Balloon Angioplasty (POBA) regarding treatment of high-grade stenoses ≥ 75 % in the infrapopliteal arteries (located below the P3 segment of the popliteal artery to the tibiotalar joint) in patients presenting with chronic limb-threatening ische-mia (CLTI) (Rutherford 4-6).

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years at the time of consent.
2. Subject has been informed of the nature of the study, is willing to comply with all required follow-up evaluations within the defined follow-up visit windows and has signed an Ethics Committee (EC) approved consent form.
3. Female subjects of childbearing potential have a negative pregnancy test ≤ 7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation. Female subjects will be exempted from this requirement in case they are sterile, infertile, or have been post-menopausal for at least 12 months (no menses).
4. Life expectancy \> 1 year in the investigator's opinion.
5. Subject presenting with documented chronic limb-threatening ischemia (CLTI) in the target limb defined as Rutherford category 4, 5 or 6.
6. In case of Rutherford category 5 or 6: Subjects with documented infection grade ≤ 2 according to the wound ischemia foot infection (WIfI) classification.
7. All ischemia grades according to the wound ischemia foot infection (WIfI) classifi-cation are allowed.documented infection grade ≤ 2 according to the wound ischemia foot infection (WIfI) classification.

7. All ischemia grades according to the wound ischemia foot infection (WIfI) classification are allowed.

8. Reference Vessel Diameter (RVD) ≥ 2 and ≤ 4.0 mm. 9. ≥ 75 % stenosis or occlusion of the target vessel by visual estimate of the treating physician; no minimal lesion length required.

10. The target lesion may consist of multiple target vessel lesions, if they are ≤ 5 cm away from each other and if at least one of them is a stenosis ≥ 75 % and all lesions are located in only one of the infrapopliteal arteries or directly within the transition area. Non-target vessels (e.g. inflow lesions or contralateral extremity, other non-target vessels below the knee) and non-target lesions of the target ves-sel can be treated during the study index procedure but according to the patient's randomization result (interventional group: Sirolimus-coated balloon or POBA; control group: only POBA).

11. No lesion length limitation, no limitation in number of used devices. 12. The lesion must be located in the infrapopliteal arteries and above the ankle joint. Lesions may not be located above the tibioperoneal trunk or below the tibiotalar joint (arteries of the foot), nor can the treatment (investigational device or standard PTA, including pre-dilatation) extend beyond these indicated regions for more than 1 cm. Note: A target lesion can extend into the P3 segment in case it involves a straight uninterrupted lesion extending from the target vessel.

13. Presence of documented run-off to the foot (clearly visible at least one of the following run-off vessels: dorsalis pedis or pedal arch or plantar arteries by angiography). The target vessel should give direct or indirect run-off to the foot.

14. Inflow free from flow-limiting lesion confirmed by angiography. Patients with flow-limiting inflow lesions (≥ 50 % stenosis) can be included if the lesion(s) have been treated successfully before enrollment, with a maximum residual stenosis of ≤ 30 % per visual assessment. If an inflow lesion must be treated within or above the P3 segment of the popliteal artery, there must be a minimum of 3 cm healthy tissue between this (treated) lesion and the infrapopliteal target lesion. Use of paclitaxel-coated devices is not permitted.

15. Successful pre-dilatation of the (entire) target lesion. Success being documented by angiographic visual estimate of ≤ 50 % residual diameter stenosis of the target lesion and no flow limiting dissection (\< Grade D dissection).

16. Participants can only be enrolled once with a single target lesion.

Exclusion criteria:

1. Subjects with major amputation of the target leg above the ankle joint.
2. Planned index limb major amputation above the ankle joint, or any other planned major surgery within 30 days pre- or post-procedure. A planned amputation includ-ing and below the ankle is accepted.
3. Recent MI or stroke \< 30 days prior to the index procedure.
4. Any vascular treatment with PTX or sirolimus-coated devices 60 days prior to index procedure
5. Known or suspected active infection at the time of the index procedure (abnormal white blood cell count, fever, sepsis or positive blood culture), excluding an infection of a lower extremity wound on the target limb (corresponding to WIfI infection grad 3)
6. Subjects with neurotrophic ulcers, heel pressure ulcers or calcaneal ulcers with a risk for major amputation regarding the study leg; Subjects with uncomplicated ulcers can be included.
7. Subjects with documented active osteomyelitis of the study leg, excluding the phalanges and metatarsalia, that is beyond cortical involvement of the bone per clinical judgment
8. Subjects with systemic vasculitis, such as Lupus Erythematosus or polymyalgia rheumatica on active treatment.
9. Subjects receiving systemic corticosteroid therapy (expected dosage \> 5 mg of prednisolone or equivalent, per day, during the initial 9 months after procedure) or other systemic immunosuppressant therapy.
10. Known allergies or sensitivities to heparin, aspirin (ASA), other anticoagulant/antiplatelet therapies which could not be substituted, and/or sirolimus or an allergy to contrast media that cannot be adequately pre-treated prior to the index procedure.
11. The subject is currently enrolled in another investigational device, drug or biological trial.
12. Female subjects who are breast feeding at the time of enrollment
13. Significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy
14. Prior stent(s) or bypass surgery with safety margin \< 3 cm within the target vessel (including stents placed within target vessels during the index procedure prior to randomization).
15. Previous procedure with drug-coated balloons in the target vessel within 6 months prior to index procedure.
16. Stenosis ≥ 75 % or occlusions (target lesion) located or extending in the popliteal artery or below the ankle joint space. Note: A target lesion can extend into the P3 segment in case it involves a straight lesion extending from the target vessel. Non-significant stenosis below the ankle joint can be allowed in case this is not part of the target lesion.
17. Untreated significant (≥ 50 % residual stenosis measured by Duplex Sonography) inflow lesion or occlusion in the ipsilateral iliac, SFA and popliteal arteries.
18. Failure to obtain a ≤ 30 % residual stenosis in pre-existing, hemodynamically sig-nificant (≥ 50 % measured by Duplex Sonography) inflow lesions in the ipsilateral iliac, SFA and popliteal artery.
19. Aneurysm in the target vessel.
20. Angiographic evidence of thrombus within target vessel.
21. Pre-dilatation resulted in a major (≥ Grade D) flow-limiting dissection (observed on 2 orthogonal views) or residual stenosis \> 50 %.
22. Use of alternative therapy, e.g. atherectomy, scoring balloon, laser, radiation therapy, stents as part of target vessel treatment. Note: Use of stents is only allowed for bailout stenting.

Primary outcomes:
measure: composite of limb salvage and primary patency at 6 months
timeFrame: 6 months after study procedure (PTA with medical product under investigation or comparator)
Secondary outcomes:
measure: MALE-POD
timeFrame: 30 days after study procedure.
measure: rate of clinically-driven TVR
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: TVR rate in treated target vessel and non-target vessels
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: TVR rate
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Primary Patency rate
timeFrame: 1, 6, 24 and 36 months after study procedure.
measure: Primary Patency of target and treat non-target vessel
timeFrame: 1, 6, 24 and 36 months after study procedure.
measure: Secondary Patency rate
timeFrame: 1, 6, 24 and 36 months after study procedure.
measure: Secondary Patency of target and treat non-target vessel
timeFrame: 1, 6, 24 and 36 months after study procedure.
measure: Re-stenosis of >= 75% or occlusion rate
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Number of treated Non-target vessels
timeFrame: 36 months after study procedure
measure: Walking Capacity Assessment 1
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Walking Capacity Assessment 2
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Target Limb Major Amputations
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: all-cause mortality
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Amputation free survival (AFS)
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Amputation free survival and resolved CLTI
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Ankle-Brachial-Index (ABI)
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Toe-Brachial-Index (TBI)
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Rutherford classification
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Primary sustained clinical improvement
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Secondary sustained clinical improvement
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: EQ-5D-3L
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Wound healing
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: New or recurrent wound of the target limb
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Length of in-hospital-stay
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Major Adverse Limb Events (MALE)
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: Device Success
timeFrame: at index procedure
measure: Technical Success
timeFrame: at index procedure
measure: Procedural success
timeFrame: at index procedure
measure: composite endpoint: patency, rate of overall-cause death and amputation-free survival
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
measure: composite endpoint: rate of all-cause death, target limb major amputation and clinically-driven TLR
timeFrame: 1, 6, 12, 24 and 36 months after study procedure.
Other outcomes:
Locations:
city: Wien
country: Austria
facility: AKH Wien, Universitätsklinik für Innere Medizin II, Klinische Abteilung für Angiologie
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien (Wien AKH), Department of Radiology
city: Wien
country: Austria
facility: Hanusch-Krankenhaus
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen, Diagnostic and Interventional Radiology
state: Baden-Württemberg
city: Bad Oeynhausen
country: Germany
facility: Heart and Diabetes Center North Rhine Westphalia, Clinic for General and Interventional Cardiology/Angiology
state: North Rhine Westphalia
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg-Bad Krozingen; Clinic for Cardiology and Angiology II
city: Brandenburg
country: Germany
facility: Universitätsklinikum Brandenburg, Abteilung für Innere Medizin 1, Hochschulklinik für Angiologie
city: Bruchsal
country: Germany
facility: Fürst-Stirum-Klinik Bruchsal, Klinik für Kardiologie, Angiologie, Diabetologie, Neurologie und Intensivmedizin
city: Flensburg
country: Germany
facility: DIAKO gGmbH, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Universitäres Herz- und Gefäßzentrum Hamburg, Klinik und Poliklinik für Gefäßmedizin
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Medizinische Klinik III, Kardiologie, Angiologie und Pneumologie
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Institut für Diagnostische und Interventionelle Radiologie
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Lingen
country: Germany
facility: Bonifatius-Hospital Lingen (Ems)
city: Münster
country: Germany
facility: St. Franziskus-Hospital GmbH Klinik für Gefäßchirurgie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Kardiologie I, Koronare Herzkrankheit, Herzinsuffizienz und Angiologie
city: Radebeul
country: Germany
facility: Elblandklinikum Radebeul, Gefäßzentrum
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brüder Regensburg, Institut für Radiologie, Neuroradiologie und Nuklearmedizin
city: Rendsburg
country: Germany
facility: Schön Klinik Rendsburg, Institut für Diagnostische und Interventionelle Radiologie/Neuroradiologie
city: Riesa
country: Germany
facility: Elblandklinikum Riesa, Gefäßzentrum
city: Sonneberg
country: Germany
facility: MEDINOS-Kliniken Sonneberg, Gefäßzentrum
city: Torgau
country: Germany
facility: Kreiskrankenhaus Torgau
city: Weinheim
country: Germany
facility: GRN Klinik Weinheim, Kardiologie/Angiologie
Study officials:
affiliation: University Hospital Jena, Institute of Radiology
name: Ulf Teichgraeber, Prof. Dr.
role: STUDY_DIRECTOR
References:
citation: Teichgraber U, Platzer S, Lehmann T, Ingwersen M, Aschenbach R, Beschorner U, Scheinert D, Zeller T. Sirolimus-Coated Balloon Angioplasty of Infra-popliteal Lesions for the Treatment of Chronic Limb-Threatening Ischemia: Study Protocol for the Randomized Controlled LIMES Study. Cardiovasc Intervent Radiol. 2022 Nov;45(11):1716-1724. doi: 10.1007/s00270-022-03213-z. Epub 2022 Jul 29.