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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04772300
Recruitment Status : Recruiting
First Posted : February 26, 2021
Last Update Posted : April 6, 2022
Sponsor:
Collaborators:
Concept Medical Inc.
VascuScience GmbH
CoreLab Black Forest
Center for Clinical Studies, University Hospital Jena
Information provided by (Responsible Party):
Ulf Teichgräber, Jena University Hospital

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 infrapopliteal artery disease.


Condition or disease Intervention/treatment Phase
Peripheral Artery Disease Combination Product: Percutaneous Transluminal Angioplasty (PTA) MagicTouch Sirolimus Coated PTA Balloon Catheter Device: Percutaneous Transluminal Angioplasty (PTA) with non-coated balloon catheter (POBA) Not Applicable

Detailed Description:
The primary 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 noninferior to Plain Old Balloon Angioplasty (POBA) regarding treatment of occlusions in the infrapopliteal arteries (located below the P3 segment of the popliteal artery to the tibiotalar joint) in patients pre-senting with chronic limb-threatening ischemia (CLTI) (Rutherford 4-6).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1:1-randomization, parallel design, stratified by center.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 10, 2022
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : July 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Sirolimus

Arm Intervention/treatment
Experimental: Sirolimus DCB group
Intervention with Sirolimus-coated balloon catheter
Combination Product: Percutaneous Transluminal Angioplasty (PTA) MagicTouch Sirolimus Coated PTA Balloon Catheter
PTA with an sirolimus drug-coated balloon catheter (SRL-DCB) in the infrapopliteal artery

Active Comparator: POBA group
Intervention with non-coated balloon catheter (POBA)
Device: Percutaneous Transluminal Angioplasty (PTA) with non-coated balloon catheter (POBA)
PTA with an non-coated balloon catheter (POBA) in the infrapopliteal artery




Primary Outcome Measures :
  1. composite of limb salvage and primary patency at 6 months [ Time Frame: 6 months after study procedure (PTA with medical product under investigation or comparator) ]

    composite of limb salvage and primary patency at 6 months. Patency is defined as the absence of target lesion occlusion (no flow) as determined by duplex ultrasound and/or absence of clinically-driven TLR revascularization (CD-TLR), where clinically-driven is defined as a restenosis of ≥ 70 % in the target lesion with

    • Wound persistence and/or
    • Increase in size of pre-existing wounds and/or
    • Occurrence of new wounds and/or
    • Deterioration of Rutherford Class


Secondary Outcome Measures :
  1. MALE-POD [ Time Frame: 1 month after study procedure. ]

    Major Adverse Limb Events (MALE) with perioperative death (POD) after 1 month. 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.


  2. rate of clinically-driven TVR [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    occurrence of clinically-driven TVR at certain time points

  3. TVR rate in treated target vessel and non-target vessels [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Rate of all TVR including treated non-target vessel at 1, 6, 12, 24 and 36 months.

  4. TVR rate [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Rate of all TVR at 1, 6, 12, 24 and 36 months.

  5. Primary Patency rate [ Time Frame: 1, 6, 24 and 36 months after study procedure. ]
    Primary Patency rate at certain time points

  6. Primary Patency of target and treat non-target vessel [ Time Frame: 1, 6, 24 and 36 months after study procedure. ]
    Primary Patency rate of target and treat non-target vessel at certain time points

  7. Secondary Patency rate [ Time Frame: 1, 6, 24 and 36 months after study procedure. ]
    Secondary Patency rate at certain time points

  8. Secondary Patency of target and treat non-target vessel [ Time Frame: 1, 6, 24 and 36 months after study procedure. ]
    Secondary Patency rate of target and treat non-target vessel at certain time points

  9. Re-occlusion rate [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Rate of re-occlusion at certain time points, defined as the absence of flow in the target vessel as determined by duplex ultrasound

  10. Number of treated Non-target vessels [ Time Frame: 36 months after study procedure ]
    Number of treated Non-target vessels

  11. Walking Capacity Assessment 1 [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    patient-self-assessment of walking distance at certain time points

  12. Walking Capacity Assessment 2 [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    VascuQoL questionnaire (Vascular Quality of Life Questionnaire) at certain time points; 25 questions (scale 1 to 7); best score 175, worst score 25.

  13. Target Limb Major Amputations [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Rate of target limb major amputations at certain time points

  14. all-cause mortality [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Rate of all-cause death at certain time points

  15. Amputation free survival (AFS) [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Amputation free survival (AFS) at certain time points

  16. Amputation free survival and resolved CLTI [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Amputation free survival and resolved CLTI at certain time points

  17. Ankle-Brachial-Index (ABI) [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Change in ankle-brachial index (ABI) from pre-procedure to certain time points

  18. Toe-Brachial-Index (TBI) [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Change in toe-brachial index (TBI) from pre-procedure to certain time points

  19. Rutherford classification [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Change in Rutherford category from pre-procedure to certain time points

  20. Primary sustained clinical improvement [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    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

  21. Secondary sustained clinical improvement [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    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

  22. EQ-5D-3L [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    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.

  23. Wound healing [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Rate of wound healing from pre-procedure to certain time points

  24. New or recurrent wound of the target limb [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    New or recurrent wound of the target limb from pre-procedure to certain time points

  25. Change in VascuQoL [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Walking capacity assessment by VascuQoL from pre-procedure to certain time points. 25 questions (scale 1 to 7); best score 175, worst score 25.

  26. Length of in-hospital-stay [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    Days of hospitalization at certain time points

  27. Major Adverse Limb Events (MALE) [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    MALE at certain time points

  28. Device Success [ Time Frame: at index procedure ]
    Device Success defined as exact deployment of the device according to the instructions for use

  29. Technical Success [ Time Frame: at index procedure ]
    Technical Success defined as successful vascular access and completion of the endovascular procedure and immediate morphological success with ≤ 50 % residual diameter reduction of the treated lesion on completion angiography

  30. Procedural success [ Time Frame: at index procedure ]
    Procedural success, defined as combination of technical success, device success and absence of procedural complications

  31. composite endpoint: patency, rate of overall-cause death and amputation-free survival [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    composite endpoint consisting of patency, rate of overall-cause death and amputation-free survival at certain time points

  32. composite endpoint: rate of all-cause death, target limb major amputation and clinically-driven TLR [ Time Frame: 1, 6, 12, 24 and 36 months after study procedure. ]
    composite endpoint consisting of rate of all-cause death, target limb major amputation and clinically-driven Target Lesion Revascularization at certain time points



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 0-2 and/or ischemia grade 2-3 according to the wound ischemia foot infection (WIfI) classification.
  7. Reference Vessel Diameter (RVD) ≥ 2 and ≤ 4.0 mm.
  8. Total occlusion (100 % stenosis) of the target vessel; no minimal lesion length required.
  9. 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.
  10. Non-target vessels (e.g. inflow lesions or contralateral extremity) 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 extend above the tibioperoneal trunk (P3 segment of the popliteal artery) 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. 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.
  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.
  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). TL is not considered non-dilatable by the operator due to concentric, circumferential calcium and TL can be treated successfully by balloon angioplasty without the need for bail-out stenting.

Exclusion Criteria:

  1. Subjects with amputation of the target leg above the metatarsal level.
  2. Planned index limb amputation above the metatarsal level, or any other planned major surgery within 30 days pre- or post-procedure. A planned amputation including and below the metatarsal level (1 or multiple rays) is accepted.
  3. Recent MI or stroke < 30 days prior to the index procedure.
  4. 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 (only WIfI infection grade 0-2 allowed).
  5. Subjects with infection grade 3 and ischemia grade 0 and/or 1 according to WIfI classification.
  6. Subjects with neurotrophic ulcers, heel pressure ulcers or calcaneal ulcers with a risk for major amputation; Subjects with uncomplicated ulcers can be included.
  7. Subjects with documented active osteomyelitis, excluding the phalanges, that is beyond cortical involvement of the bone per clinical judgment.
  8. Subjects with vasculitis, systemic 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).
  10. Known allergies or sensitivities to heparin, aspirin (ASA), other anticoagulant/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.
  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 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. Occlusions 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.
  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 significant (≥ 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04772300


Contacts
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Contact: Ulf Teichgrarber, Prof. Dr. +49 3641 ext 9 324806 ulf.teichgraeber@med.uni-jena.de
Contact: Laura Graziani, M.A. +49 3641 ext 9 324910 laura.graziani@med.uni-jena.de

Locations
Show Show 19 study locations
Sponsors and Collaborators
Jena University Hospital
Concept Medical Inc.
VascuScience GmbH
CoreLab Black Forest
Center for Clinical Studies, University Hospital Jena
Investigators
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Study Director: Ulf Teichgraeber, Prof. Dr. University Hospital Jena, Institute of Radiology
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Responsible Party: Ulf Teichgräber, Principal Coordinating Investigator, Jena University Hospital
ClinicalTrials.gov Identifier: NCT04772300    
Other Study ID Numbers: ZKSJ0132
First Posted: February 26, 2021    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ulf Teichgräber, Jena University Hospital:
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
Additional relevant MeSH terms:
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Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs