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 (LIMES)
Primary Purpose
Peripheral Artery Disease
Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Percutaneous Transluminal Angioplasty (PTA) MagicTouch Sirolimus Coated PTA Balloon Catheter
Percutaneous Transluminal Angioplasty (PTA) with non-coated balloon catheter (POBA)
Sponsored by
About this trial
This is an interventional treatment trial for Peripheral Artery Disease focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years at the time of consent.
- 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.
- 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).
- Life expectancy > 1 year in the investigator's opinion.
- Subject presenting with documented chronic limb-threatening ischemia (CLTI) in the target limb defined as Rutherford category 4, 5 or 6.
- In case of Rutherford category 5 or 6: Subjects with documented infection grade ≤ 2 according to the wound ischemia foot infection (WIfI) classification.
- All ischemia grades according to the wound ischemia foot infection (WIfI) classification are allowed.
- Reference Vessel Diameter (RVD) ≥ 2 and ≤ 4.0 mm.
- Total occlusion (100 % stenosis) of the target vessel; no minimal lesion length required.
- 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 occluded 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 vessel can be treated during the study index procedure but according to the patient's ran-domization result (interventional group: Sirolimus-coated balloon or POBA; control group: only POBA).
- No lesion length limitation, no limitation in number of used devices.
- The lesion must be located in the infrapopliteal arteries and above the ankle joint. Lesions may not extend 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.
- 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.
- 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.
- 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).
- Participants can only be enrolled once with a single target lesion.
Exclusion Criteria:
- Subjects with major amputation of the target leg above the ankle joint.
- 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 including and below the ankle is accepted.
- Recent MI or stroke < 30 days prior to the index procedure.
- 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 grade 3)
- 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.
- 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
- Subjects with systemic vasculitis, such as Lupus Erythematosus or polymyalgia rheumatica on active treatment.
- 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.
- Known allergies or sensitivities to heparin, aspirin (ASA), other anticoagu-lant/anti-platelet 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.
- The subject is currently enrolled in another investigational device, drug or biological trial.
- Female subjects who are breast feeding at the time of enrollment
- Significant gastrointestinal bleeding or any coagulopathy that would contraindi-cate the use of anti-platelet therapy
- 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 pri-or to randomization).
- Previous procedure with drug-coated balloons in the target vessel within 6 months prior to index procedure.
- 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 and does not require treatment.
- Untreated significant (≥ 50 % residual stenosis measured by Duplex Sonogra-phy) inflow lesion or occlusion in the ipsilateral iliac, SFA and popliteal arteries.
- Failure to obtain a ≤ 30 % residual stenosis in pre-existing, hemodynamically significant (≥ 50 % measured by Duplex Sonography) inflow lesions in the ipsilateral iliac, SFA and popliteal artery.
- Aneurysm in the target vessel.
- Angiographic evidence of thrombus within target vessel.
- Pre-dilatation resulted in a major (≥ Grade D) flow-limiting dissection (observed on 2 orthogonal views) or residual stenosis > 50 %.
- 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.
Sites / Locations
- AKH Wien, Universitätsklinik für Innere Medizin II, Klinische Abteilung für AngiologieRecruiting
- Allgemeines Krankenhaus der Stadt Wien (Wien AKH), Department of RadiologyRecruiting
- Hanusch-KrankenhausRecruiting
- University Hospital Tuebingen, Diagnostic and Interventional Radiology
- Heart and Diabetes Center North Rhine Westphalia, Clinic for General and Interventional Cardiology/Angiology
- Herz- und Gefäßzentrum Bad Bevensen
- Universitäts-Herzzentrum Freiburg-Bad Krozingen; Clinic for Cardiology and Angiology II
- Fürst-Stirum-Klinik Bruchsal, Klinik für Kardiologie, Angiologie, Diabetologie, Neurologie und IntensivmedizinRecruiting
- DIAKO gGmbH, Institut für Diagnostische und Interventionelle Radiologie und NeuroradiologieRecruiting
- Universitätsklinikum Heidelberg, Medizinische Klinik III, Kardiologie, Angiologie und Pneumologie
- University Hospital JenaRecruiting
- University Hospital LeipzigRecruiting
- Bonifatius-Hospital Lingen (Ems)
- Marienhaus Klinikum Mainz, Klinik für Diagnostische und Interventionelle RadiologieRecruiting
- Gefäßpraxis im TalRecruiting
- St. Franziskus-Hospital GmbH, Klinik für GefäßchirurgieRecruiting
- Universitätsklinikum Münster, Klinik für Kardiologie I, Koronare Herzkrankheit, Herzinsuffizienz und AngiologieRecruiting
- Elblandklinikum Radebeul, GefäßzentrumRecruiting
- Krankenhaus Barmherzige Brüder Regensburg, Institut für Radiologie, Neuroradiologie und NuklearmediziRecruiting
- Imland Klinik Rendsburg, Institut für Diagnostische und Interventionelle Radiologie/NeuroradiologieRecruiting
- Elblandklinikum Riesa, GefäßzentrumRecruiting
- RoMed Klinikum Rosenheim, Diagnostische und Interventionelle RadiologieRecruiting
- MEDINOS-Kliniken Sonneberg, GefäßzentrumRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sirolimus DCB group
POBA group
Arm Description
Intervention with Sirolimus-coated balloon catheter
Intervention with non-coated balloon catheter (POBA)
Outcomes
Primary Outcome Measures
composite of limb salvage and primary patency at 6 months
composite of limb salvage and primary patency at 6 months. Primary patency is defined as absence of target lesion restenosis ≥ 75 % or re-occlu-sion with restoration of in-line flow to the ankle as determined by duplex ultrasound without clinically driven target lesion revascularization (CD-TLR) after index procedure.
Clinically driven TLR is defined as revascularization due to restenosis of ≥ 50 % in the target lesion and
Deterioration of Rutherford Class and/or
Deterioration or persistence of wounds according to the WIfI classification wound component score
Secondary Outcome Measures
MALE-POD
Major Adverse Limb Events (MALE) with perioperative all-cause death (POD) at 30 days Major Adverse Limb Events (MALE) are defined as above-ankle amputation or major reintervention (i.e., new bypass graft, interposition graft revision, or thrombectomy/thrombolysis) of the treated limb involving a BTK artery.
Perioperative death (POD) is defined as death within 30 days after index proce-dure.
Major Adverse Limb Events (MALE) are defined as above-ankle amputation or major reintervention (i.e., new bypass graft, interposition graft revision, or thrombectomy/thrombolysis) of the treated limb involving a BTK artery.
Perioperative death (POD) is defined as death within 30 days after index procedure.
rate of clinically-driven TVR
occurrence of clinically-driven TVR at certain time points
TVR rate in treated target vessel and non-target vessels
Rate of all TVR including treated non-target vessel at 1, 6, 12, 24 and 36 months.
TVR rate
Rate of all TVR at 1, 6, 12, 24 and 36 months.
Primary Patency rate
Primary Patency rate at certain time points
Primary Patency of target and treat non-target vessel
Primary Patency rate of target and treat non-target vessel at certain time points
Secondary Patency rate
Secondary Patency rate at certain time points
Secondary Patency of target and treat non-target vessel
Secondary Patency rate of target and treat non-target vessel at certain time points
Re-stenosis of >= 75% or occlusion rate
Rate of re-stenosis or re-occlusion at certain time points, defined as the absence of flow in the target vessel as determined by duplex ultrasound
Number of treated Non-target vessels
Number of treated Non-target vessels
Walking Capacity Assessment 1
patient-self-assessment of walking distance at certain time points
Walking Capacity Assessment 2
VascuQoL questionnaire (Vascular Quality of Life Questionnaire) at certain time points; 25 questions (scale 1 to 7); best score 175, worst score 25.
Target Limb Major Amputations
Rate of target limb major amputations at certain time points
all-cause mortality
Rate of all-cause death at certain time points
Amputation free survival (AFS)
Amputation free survival (AFS) at certain time points
Amputation free survival and resolved CLTI
Amputation free survival and resolved CLTI at certain time points
Ankle-Brachial-Index (ABI)
Change in ankle-brachial index (ABI) from pre-procedure to certain time points
Toe-Brachial-Index (TBI)
Change in toe-brachial index (TBI) from pre-procedure to certain time points
Rutherford classification
Change in Rutherford category from pre-procedure to certain time points
Primary sustained clinical improvement
improvement shift in the Rutherford Category of one class or more in amputation free surviving patients without the need for clinically driven TVR at certain time points
Secondary sustained clinical improvement
improvement shift in the Rutherford classification of one class or more in amputation free surviving patients including those with clinically driven TVR at certain time points
EQ-5D-3L
Change in EQ-5D-3L (Quality of Life questionnaire) from pre-procedure to certain time points; 5 questions (scale 1 to 3), best score 5, worst score 15.
Wound healing
Rate of wound healing from pre-procedure to certain time points
New or recurrent wound of the target limb
New or recurrent wound of the target limb from pre-procedure to certain time points
Length of in-hospital-stay
Days of hospitalization at certain time points
Major Adverse Limb Events (MALE)
MALE at certain time points
Device Success
Device Success defined as exact deployment of the device according to the instructions for use
Technical Success
Technical success defined as successful vascular access and completion of the endovascular procedure with <= 50% residual diameter stenosis and restoration of in-line flow to the ankle
Procedural success
30) Procedural success, defined as combination of technical success, device suc-cess and absence of major adverse events (MALE-POD, myocardial infarction, stroke) within 72 h of the index procedure).
composite endpoint: patency, rate of overall-cause death and amputation-free survival
composite endpoint consisting of patency, rate of overall-cause death and amputation-free survival at certain time points
composite endpoint: rate of all-cause death, target limb major amputation and clinically-driven TLR
composite endpoint consisting of rate of all-cause death, target limb major amputation and clinically-driven Target Lesion Revascularization at certain time points
Full Information
NCT ID
NCT04772300
First Posted
February 23, 2021
Last Updated
March 10, 2023
Sponsor
Jena University Hospital
Collaborators
Concept Medical Inc., VascuScience GmbH, CoreLab Black Forest, Center for Clinical Studies, University Hospital Jena
1. Study Identification
Unique Protocol Identification Number
NCT04772300
Brief Title
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
Acronym
LIMES
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2022 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
July 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jena University Hospital
Collaborators
Concept Medical Inc., VascuScience GmbH, CoreLab Black Forest, Center for Clinical Studies, University Hospital Jena
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
1:1-randomization, parallel design, stratified by center.
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
230 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sirolimus DCB group
Arm Type
Experimental
Arm Description
Intervention with Sirolimus-coated balloon catheter
Arm Title
POBA group
Arm Type
Active Comparator
Arm Description
Intervention with non-coated balloon catheter (POBA)
Intervention Type
Combination Product
Intervention Name(s)
Percutaneous Transluminal Angioplasty (PTA) MagicTouch Sirolimus Coated PTA Balloon Catheter
Intervention Description
PTA with an sirolimus drug-coated balloon catheter (SRL-DCB) in the infrapopliteal artery
Intervention Type
Device
Intervention Name(s)
Percutaneous Transluminal Angioplasty (PTA) with non-coated balloon catheter (POBA)
Intervention Description
PTA with an non-coated balloon catheter (POBA) in the infrapopliteal artery
Primary Outcome Measure Information:
Title
composite of limb salvage and primary patency at 6 months
Description
composite of limb salvage and primary patency at 6 months. Primary patency is defined as absence of target lesion restenosis ≥ 75 % or re-occlu-sion with restoration of in-line flow to the ankle as determined by duplex ultrasound without clinically driven target lesion revascularization (CD-TLR) after index procedure.
Clinically driven TLR is defined as revascularization due to restenosis of ≥ 50 % in the target lesion and
Deterioration of Rutherford Class and/or
Deterioration or persistence of wounds according to the WIfI classification wound component score
Time Frame
6 months after study procedure (PTA with medical product under investigation or comparator)
Secondary Outcome Measure Information:
Title
MALE-POD
Description
Major Adverse Limb Events (MALE) with perioperative all-cause death (POD) at 30 days Major Adverse Limb Events (MALE) are defined as above-ankle amputation or major reintervention (i.e., new bypass graft, interposition graft revision, or thrombectomy/thrombolysis) of the treated limb involving a BTK artery.
Perioperative death (POD) is defined as death within 30 days after index proce-dure.
Major Adverse Limb Events (MALE) are defined as above-ankle amputation or major reintervention (i.e., new bypass graft, interposition graft revision, or thrombectomy/thrombolysis) of the treated limb involving a BTK artery.
Perioperative death (POD) is defined as death within 30 days after index procedure.
Time Frame
30 days after study procedure.
Title
rate of clinically-driven TVR
Description
occurrence of clinically-driven TVR at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
TVR rate in treated target vessel and non-target vessels
Description
Rate of all TVR including treated non-target vessel at 1, 6, 12, 24 and 36 months.
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
TVR rate
Description
Rate of all TVR at 1, 6, 12, 24 and 36 months.
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Primary Patency rate
Description
Primary Patency rate at certain time points
Time Frame
1, 6, 24 and 36 months after study procedure.
Title
Primary Patency of target and treat non-target vessel
Description
Primary Patency rate of target and treat non-target vessel at certain time points
Time Frame
1, 6, 24 and 36 months after study procedure.
Title
Secondary Patency rate
Description
Secondary Patency rate at certain time points
Time Frame
1, 6, 24 and 36 months after study procedure.
Title
Secondary Patency of target and treat non-target vessel
Description
Secondary Patency rate of target and treat non-target vessel at certain time points
Time Frame
1, 6, 24 and 36 months after study procedure.
Title
Re-stenosis of >= 75% or occlusion rate
Description
Rate of re-stenosis or re-occlusion at certain time points, defined as the absence of flow in the target vessel as determined by duplex ultrasound
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Number of treated Non-target vessels
Description
Number of treated Non-target vessels
Time Frame
36 months after study procedure
Title
Walking Capacity Assessment 1
Description
patient-self-assessment of walking distance at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Walking Capacity Assessment 2
Description
VascuQoL questionnaire (Vascular Quality of Life Questionnaire) at certain time points; 25 questions (scale 1 to 7); best score 175, worst score 25.
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Target Limb Major Amputations
Description
Rate of target limb major amputations at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
all-cause mortality
Description
Rate of all-cause death at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Amputation free survival (AFS)
Description
Amputation free survival (AFS) at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Amputation free survival and resolved CLTI
Description
Amputation free survival and resolved CLTI at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Ankle-Brachial-Index (ABI)
Description
Change in ankle-brachial index (ABI) from pre-procedure to certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Toe-Brachial-Index (TBI)
Description
Change in toe-brachial index (TBI) from pre-procedure to certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Rutherford classification
Description
Change in Rutherford category from pre-procedure to certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Primary sustained clinical improvement
Description
improvement shift in the Rutherford Category of one class or more in amputation free surviving patients without the need for clinically driven TVR at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Secondary sustained clinical improvement
Description
improvement shift in the Rutherford classification of one class or more in amputation free surviving patients including those with clinically driven TVR at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
EQ-5D-3L
Description
Change in EQ-5D-3L (Quality of Life questionnaire) from pre-procedure to certain time points; 5 questions (scale 1 to 3), best score 5, worst score 15.
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Wound healing
Description
Rate of wound healing from pre-procedure to certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
New or recurrent wound of the target limb
Description
New or recurrent wound of the target limb from pre-procedure to certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Length of in-hospital-stay
Description
Days of hospitalization at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Major Adverse Limb Events (MALE)
Description
MALE at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
Device Success
Description
Device Success defined as exact deployment of the device according to the instructions for use
Time Frame
at index procedure
Title
Technical Success
Description
Technical success defined as successful vascular access and completion of the endovascular procedure with <= 50% residual diameter stenosis and restoration of in-line flow to the ankle
Time Frame
at index procedure
Title
Procedural success
Description
30) Procedural success, defined as combination of technical success, device suc-cess and absence of major adverse events (MALE-POD, myocardial infarction, stroke) within 72 h of the index procedure).
Time Frame
at index procedure
Title
composite endpoint: patency, rate of overall-cause death and amputation-free survival
Description
composite endpoint consisting of patency, rate of overall-cause death and amputation-free survival at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
Title
composite endpoint: rate of all-cause death, target limb major amputation and clinically-driven TLR
Description
composite endpoint consisting of rate of all-cause death, target limb major amputation and clinically-driven Target Lesion Revascularization at certain time points
Time Frame
1, 6, 12, 24 and 36 months after study procedure.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years at the time of consent.
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.
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).
Life expectancy > 1 year in the investigator's opinion.
Subject presenting with documented chronic limb-threatening ischemia (CLTI) in the target limb defined as Rutherford category 4, 5 or 6.
In case of Rutherford category 5 or 6: Subjects with documented infection grade ≤ 2 according to the wound ischemia foot infection (WIfI) classification.
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:
Subjects with major amputation of the target leg above the ankle joint.
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.
Recent MI or stroke < 30 days prior to the index procedure.
Any vascular treatment with PTX or sirolimus-coated devices 60 days prior to index procedure
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)
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.
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
Subjects with systemic vasculitis, such as Lupus Erythematosus or polymyalgia rheumatica on active treatment.
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.
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.
The subject is currently enrolled in another investigational device, drug or biological trial.
Female subjects who are breast feeding at the time of enrollment
Significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy
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).
Previous procedure with drug-coated balloons in the target vessel within 6 months prior to index procedure.
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.
Untreated significant (≥ 50 % residual stenosis measured by Duplex Sonography) inflow lesion or occlusion in the ipsilateral iliac, SFA and popliteal arteries.
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.
Aneurysm in the target vessel.
Angiographic evidence of thrombus within target vessel.
Pre-dilatation resulted in a major (≥ Grade D) flow-limiting dissection (observed on 2 orthogonal views) or residual stenosis > 50 %.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ulf Teichgrarber, Prof. Dr.
Phone
+49 3641
Ext
9 324806
Email
ulf.teichgraeber@med.uni-jena.de
First Name & Middle Initial & Last Name or Official Title & Degree
Ina Kunstmann, Dr.
Phone
+49 3641
Ext
9 324853
Email
ina.kunstmann@med.uni-jena.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulf Teichgraeber, Prof. Dr.
Organizational Affiliation
University Hospital Jena, Institute of Radiology
Official's Role
Study Director
Facility Information:
Facility Name
AKH Wien, Universitätsklinik für Innere Medizin II, Klinische Abteilung für Angiologie
City
Wien
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Oliver Schlager, Prof. Dr.
Phone
+43 1 40400
Ext
46700
Email
oliver.schlager@meduniwien.ac.at
Facility Name
Allgemeines Krankenhaus der Stadt Wien (Wien AKH), Department of Radiology
City
Wien
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Floria Wolf, Prof. Dr.
Phone
+43 1 40 400
Ext
58020
Email
florian.wolf@meduniwien.ac.at
Facility Name
Hanusch-Krankenhaus
City
Wien
ZIP/Postal Code
1140
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Werner, PD Dr.
Phone
+43 1 91021
Ext
57812
Email
martin.werner@oegk.at
Facility Name
University Hospital Tuebingen, Diagnostic and Interventional Radiology
City
Tuebingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerd Grözinger, Prof. Dr.
Email
Gerd.Groezinger@med.uni-tuebingen.de
Facility Name
Heart and Diabetes Center North Rhine Westphalia, Clinic for General and Interventional Cardiology/Angiology
City
Bad Oeynhausen
State/Province
North Rhine Westphalia
ZIP/Postal Code
32545
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florian Willecke, PD Dr.
Phone
+49 5731 97
Ext
3325
Email
fwillecke@hdz-nrw.de
Facility Name
Herz- und Gefäßzentrum Bad Bevensen
City
Bad Bevensen
ZIP/Postal Code
29549
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Nolte, Dr.
Email
t.nolte@hgz-bb.de
Facility Name
Universitäts-Herzzentrum Freiburg-Bad Krozingen; Clinic for Cardiology and Angiology II
City
Bad Krozingen
ZIP/Postal Code
79189
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Zeller, Prof. Dr.
Phone
+49 7633 402
Ext
4973
Email
Thomas.Zeller@universitaets-herzzentrum.de
Facility Name
Fürst-Stirum-Klinik Bruchsal, Klinik für Kardiologie, Angiologie, Diabetologie, Neurologie und Intensivmedizin
City
Bruchsal
ZIP/Postal Code
76646
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Andrassy, Prof. Dr.
Phone
+49 7251 708
Ext
57791
Email
martin.andrassy@rkh-kliniken.de
Facility Name
DIAKO gGmbH, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie
City
Flensburg
ZIP/Postal Code
24939
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Müller-Hülsbeck, Prof. Dr.
Phone
+49 461 812
Ext
1800
Email
muehue@diako.de
Facility Name
Universitätsklinikum Heidelberg, Medizinische Klinik III, Kardiologie, Angiologie und Pneumologie
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Erbel, Prof. Dr.
Phone
+49 6221 56
Ext
8612
Email
christian.erbel@med.uni-heidelberg.de
Facility Name
University Hospital Jena
City
Jena
ZIP/Postal Code
07747
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulf Teichgraeber, Prof. Dr.
Phone
+49 3641 9
Ext
324806
Email
ulf.teichgraeber@med.uni-jena.de
Facility Name
University Hospital Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dierk Scheinert, Prof. Dr.
Phone
+49 341 97
Ext
18770
Email
Dierk.Scheinert@medizin.uni-leipzig.de
Facility Name
Bonifatius-Hospital Lingen (Ems)
City
Lingen
ZIP/Postal Code
49808
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joerg Tessarek, Dr.
Phone
+49 591
Ext
9106121
Email
Joerg.Tessarek@hospital-lingen.de
Facility Name
Marienhaus Klinikum Mainz, Klinik für Diagnostische und Interventionelle Radiologie
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jörn-Oliver Balzer, Prof. Dr.
Phone
+49 6131 57583
Ext
1700
Email
joern.balzer@marienhaus.de
Facility Name
Gefäßpraxis im Tal
City
München
ZIP/Postal Code
80331
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Britta Heilmeier, Dr.
Phone
+49 89 24215
Ext
86
Email
BrittaH@angiopraxis.de
Facility Name
St. Franziskus-Hospital GmbH, Klinik für Gefäßchirurgie
City
Münster
ZIP/Postal Code
48145
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Efthymios Beropoulis, Dr.
Phone
+49 251 935
Ext
5659
Email
efthymios.beropoulis@sfh-muenster.de
Facility Name
Universitätsklinikum Münster, Klinik für Kardiologie I, Koronare Herzkrankheit, Herzinsuffizienz und Angiologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nasser Malyar, PD Dr.
Phone
+49 251 83
Ext
47688
Email
Nasser.Malyar@ukmuenster.de
Facility Name
Elblandklinikum Radebeul, Gefäßzentrum
City
Radebeul
ZIP/Postal Code
01445
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Torsten Fuss, Dr
Phone
+49 351 833
Ext
4542
Email
torsten.fuss@elblandkliniken.de
Facility Name
Krankenhaus Barmherzige Brüder Regensburg, Institut für Radiologie, Neuroradiologie und Nuklearmedizi
City
Regensburg
ZIP/Postal Code
93049
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Niels Zorger, Prof. Dr.
Phone
+49 941 369
Ext
2500
Email
Niels.Zorger@barmherzige-regensburg.de
Facility Name
Imland Klinik Rendsburg, Institut für Diagnostische und Interventionelle Radiologie/Neuroradiologie
City
Rendsburg
ZIP/Postal Code
24768
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Wissgott, PD Dr.
Phone
+49 4331 200
Ext
6001
Email
christian.wissgott@imland.de
Facility Name
Elblandklinikum Riesa, Gefäßzentrum
City
Riesa
ZIP/Postal Code
01589
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Torsten Fuss, Dr.
Phone
+49 351 833
Ext
4542
Email
torsten.fuss@elblandkliniken.de
Facility Name
RoMed Klinikum Rosenheim, Diagnostische und Interventionelle Radiologie
City
Rosenheim
ZIP/Postal Code
83022
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gunnar Tepe, Prof. Dr.
Phone
+49 8031 365
Ext
3551
Email
gunnar.tepe@ro-med.de
Facility Name
MEDINOS-Kliniken Sonneberg, Gefäßzentrum
City
Sonneberg
ZIP/Postal Code
96515
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcus Thieme, Dr.
Phone
+49 3675 821
Ext
2012
Email
marcus.thieme@regiomed-kliniken.de
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35906491
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.
Results Reference
derived
Learn more about this trial
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
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