Back to resultsBelgian-Italian Trial to Evaluate the Efficacy and Safety of Below The Knee (BTK) Treatment With the Luminor 14 Paclitaxel Coated Percutaneous Transluminal Angioplasty Balloon Catheter of iVascular (BIBLIOS)
Primary Purpose
Peripheral Arterial Disease
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Luminor-14 Paclitaxel eluting balloon
Sponsored by
About this trial
This is an interventional treatment trial for Peripheral Arterial Disease
Eligibility Criteria
Inclusion Criteria:
- Males or non-pregnant females ≥ 18 years of age at the time of consent. Females 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 participants will be exempted from this requirement in case they are sterile, infertile or have been post-menopausal for at least 12 months
- Subject has been informed of and understands the nature of the study and provides signed informed consent to participate in the study. If the subject possesses the ability to understand and provide informed consent but due to physical inability, the subject cannot sign the informed consent form. An impartial witness may sign on behalf of the subject.
- Willing to comply with all required follow-up visits
- Rutherford Classification 5
- Significant degree of stenosis >70% or chronic total occlusion (CTO)
- Infrapopliteal lesion: P3 to the ankle-joint level (not below-the-ankle (BTA)); full length lesions or tandem lesions are allowed
- Wound, Ischemia, foot Infection (WIfI) tissue loss grade 1-2 at baseline
- WIfI foot infection grade of 0-2 at baseline
- WIfI ischemia grade 2-3 at baseline
- Estimated life expectancy ≥ 1 year
- Multiple lesions can be treated if they are located in separate vessels per standard of care but only one (1) BTK vessel can be considered as the target lesion/vessel and need to be treated according the Clinical Investigation Protocol (CIP) guidelines.
- Target vessel should give direct or indirect run-off to the foot (clearly documented in a foot/BTA angiogram)
- Patients with in-flow lesions can be included if the lesions are treated successfully (residual stenosis ≤30%) with the same drug coated balloon (DCB) platform, bail-out stenting with a bare-metal stent (BMS).
- Successful pre-dilatation of the target lesion (≤30% residual stenosis)
Exclusion Criteria:
- Previous bypass graft in the target limb
- Acute limb ischemia, defined as symptom onset during less than 14 days prior to the index procedure
- Prior or planned above-the-ankle amputation to the target limb (this does not apply to ray amputation of ≤2 digits, simple digital amputations or ulcer debridement)
- Previous DCB treatment in target vessel 6 months prior to index procedure
- WIfI tissue loss grade 0 or 3 at baseline
- WIfI foot infection grade 3 at baseline
- WIfI ischemia grade 0-1 at baseline
- Any systemic infection or immunocompromised state. Patients with an ascending infection/deep foot infection or abscess/white blood count (WBC)≥12.000/or febrile state or C reactive protein (CRP)>5mg/L
- Endovascular or surgical procedure (not including diagnostic procedures, planned simple digital amputation or wound debridement) to the target limb within 30 days after the index procedure
- Existing stent implant in the target vessel
- Use of alternative therapies: atherectomy, cutting/scoring balloons, laser, …
- Known coagulopathy, hypercoagulable state, bleeding diathesis, other blood disorder, or a platelet count less than 80.000/μL or greater than 500.000/μL
- Any subject in which antiplatelet, anticoagulant or thrombolytic therapy is contraindicated
- Myocardial infarction, coronary thrombolysis or angina less than 30 days prior to the index procedure
- History of stroke or transient ischemic attack (TIA) less than 90 days prior to the index procedure
- Known hypersensitivity or contraindication to nickel-titanium alloy (Nitinol)
- Has other comorbidities that, in the opinion of the investigator, would preclude them from receiving this treatment and/or participating in study-required follow-up
- Patients on haemodialysis
- Known hypersensitivity or allergy to contrast agents that cannot be medically managed
- Known hypersensitivity or allergy to heparin, aspirin, paclitaxel, clopidogrel or other antiplatelet/anticoagulant therapies
- Inadequate inflow lesion treatment (>30% residual stenosis)
- Inadequate result of pre-dilatation (>30% residual stenosis)
- Inadequate run-off to the foot
- Bilateral BTK enrolment in this study
Sites / Locations
- OLV Ziekenhuis Aalst
- Imelda Hospital
- A.Z. Sint-Blasius
- Z.O.L.
- AZ Groeninge
- Regionaal Ziekenhuis Heilig Hart
- Policlinico Abano Terme
- IRCCS Policlinico San Donato
- Hospital Univ. Germans Trias I Pujol
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Luminor-14 paclitaxel eluting balloon
Arm Description
Pre-dilatation of 180 seconds with a standard non-drug-coated semi-compliant balloon followed by a dilatation with a Luminor-14 paclitaxel eluting balloon (3µg/mm² balloon surface).
Outcomes
Primary Outcome Measures
Primary Efficacy Endpoint: Freedom from MALE
Freedom from major adverse limb events (MALE) defined as absence of above-ankle target limb amputation or major re-intervention to the target lesion(s) (i.e. new bypass graft, jump/interposition graft revision or thrombectomy/thrombolysis).
Primary Safety Endpoint: Freedom from MALE
freedom from major adverse limb events defined as absence of above-ankle target limb amputation or major re-intervention to the target lesion(s) (i.e. new bypass graft, jump/interposition graft revision or thrombectomy/thrombolysis).
Primary Safety Endpoint: Freedom from POD
No peri-operative death (POD) related to device, procedure or any other cause.
Secondary Outcome Measures
Target Vessel Functional Flow Assessment
Target vessel functional flow assessment defined as the presence of blood flow using duplex ultrasound. Evidence of no blood flow within the treated segment indicates loss of patency.
Freedom from clinically driven target vessel revascularisation
Freedom from clinical driven target lesion revascularization defined as absence of any reintervention due to clinical deterioration, defined as a worsening of the patient's quality of life, reflected by the health-questionnaire (EQ-5D), worsening of the Rutherford category with minimal 1 class or worsening of wound status.
Amputation free survival
Amputation free survival defined as alive with freedom from any above the ankle target limb amputation
Limb salvage
Limb salvage is defined as freedom from any above the ankle target limb amputation
Procedural success
Procedural success is defined as restoration of at least 1 below the knee artery with <30% residual stenosis in the final angiogram and outflow into the foot.
Wound healing status
Wound healing status is based on three parameters: the wound's diameter, the wound's depth and the % granulation tissue. These three parameters will be aggregated to one reported value using the modified Strauss wound classification scoring system.
Score 2: >75% red granulation tissue / <1cm² wound size / wound depth to the skin or subcutaneous.
Score 1: 50-75% red granulation tissue / 1-9cm² wound size / wound depth to muscle or tendon.
Score 0: <50% red granulation tissue / >9cm² wound size / wound depth to the bone or joint
Wound healing time
Wound healing time is defined as the number of days needed for the wound to heal completely after the index procedure.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03845543
Brief Title
Belgian-Italian Trial to Evaluate the Efficacy and Safety of Below The Knee (BTK) Treatment With the Luminor 14 Paclitaxel Coated Percutaneous Transluminal Angioplasty Balloon Catheter of iVascular
Acronym
BIBLIOS
Official Title
Belgian-Italian Prospective, Single Arm, Multicentre Study to Evaluate the Efficacy and Safety of BTK Treatment With the Luminor 14 Paclitaxel Coated Percutaneous Transluminal Angioplasty Balloon Catheter of iVascular of 150 Subjects With Critical Limb Ischemia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 28, 2018 (Actual)
Primary Completion Date
July 13, 2022 (Actual)
Study Completion Date
January 26, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ID3 Medical
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The BIBLIOS trial investigates the efficacy and safety of BTK treatment of patients suffering from critical limb ischemia (Rutherford 5) with the Luminor-14 Paclitaxel coated Percutaneous Transluminal Angioplasty Balloon catheter of iVascular. An expected total of 150 patients will be treated. Infrapopliteal lesions will be treated during this trial. The Paclitaxel eluting balloon Luminor-14 is designed for percutaneous transluminal angioplasties in which the balloon will dilate the artery upon inflation. The balloon is coated with Paclitaxel intended to avoid cellular proliferation. The drug is released by means of rapid inflation as to release a high dose in a short amount of time. Patients will be invited for a follow-up visit at 1, 6 and 12 months post-procedure. The primary efficacy endpoint is defined as freedom from major adverse limb events, defined as above the ankle target limb amputations or major reintervention to the target lesions at 6 months. The primary safety endpoint is freedom from major adverse limb event at 30 days. The secondary endpoints consist of functional flow in target vessel, freedom from clinically driven target lesion revascularisation, above the ankle amputation free survival and limb salvage at 6 and 12 months, and also procedural success, wound healing status and wound healing time.
Detailed Description
The objective of this clinical investigation is to assess the safety and efficacy of the Luminor-14 DCB for the treatment of infrapopliteal lesions patients with critical limb ischemia.
The patients will be selected based on the investigator's assessment, evaluation of the underlying disease and the eligibility criteria. The patient's medical condition should be stable, with no underlying medical condition which would prevent them from performing the required testing or from completing the study. Patients should be geographically stable, willing and able to cooperate in this clinical study, and remain available for long term follow-up. The patient is considered enrolled in the study after obtaining the patients informed consent, if there is full compliance with the study eligibility criteria and after successful guidewire passage through the study target lesion.
Prior to the index procedure the following will be collected: an informed consent for data collection, demographics, medical history, medication record, physical examination, clinical category of acute limb ischemia (Rutherford category), the resting ankle-brachial index (ABI), life quality and if applicable a wound assessment.
During the procedure the guidewire will cross the entire study lesion after which the lesion will be assessed through angiography. A pre-dilatation with a standard non-drug-coated balloon will be performed followed by a dilatation of the lesion with a Luminor-14 balloon (iVascular). If dilatation was not successful (>30% stenosis, perforation, occlusive or flow limiting dissection) prolonged inflation should be attempted after which bail-out stenting with a non-drug-coated dedicated BTK stent is allowed in case of inadequate results.
The regular follow-up is necessary to monitor the condition of the patient and the results of the procedure. Patients will be invited on weekly follow-up, with special attention to wound healing status at each visit until the wound is completely healed. The other required follow-up visits are 1,6 and 12 months follow-ups. During these visit the following data will be collected: medication record, physical exam, wound assessment and healing status, quality of life, duplex ultrasound of target vessel and possible adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Luminor-14 paclitaxel eluting balloon
Arm Type
Experimental
Arm Description
Pre-dilatation of 180 seconds with a standard non-drug-coated semi-compliant balloon followed by a dilatation with a Luminor-14 paclitaxel eluting balloon (3µg/mm² balloon surface).
Intervention Type
Device
Intervention Name(s)
Luminor-14 Paclitaxel eluting balloon
Intervention Description
Patients will be treated with the Luminor-14 paclitaxel eluting balloon
Primary Outcome Measure Information:
Title
Primary Efficacy Endpoint: Freedom from MALE
Description
Freedom from major adverse limb events (MALE) defined as absence of above-ankle target limb amputation or major re-intervention to the target lesion(s) (i.e. new bypass graft, jump/interposition graft revision or thrombectomy/thrombolysis).
Time Frame
6 months post-procedure
Title
Primary Safety Endpoint: Freedom from MALE
Description
freedom from major adverse limb events defined as absence of above-ankle target limb amputation or major re-intervention to the target lesion(s) (i.e. new bypass graft, jump/interposition graft revision or thrombectomy/thrombolysis).
Time Frame
30 days post-procedure
Title
Primary Safety Endpoint: Freedom from POD
Description
No peri-operative death (POD) related to device, procedure or any other cause.
Time Frame
30 days post-procedure
Secondary Outcome Measure Information:
Title
Target Vessel Functional Flow Assessment
Description
Target vessel functional flow assessment defined as the presence of blood flow using duplex ultrasound. Evidence of no blood flow within the treated segment indicates loss of patency.
Time Frame
6 and 12 months post-procedure
Title
Freedom from clinically driven target vessel revascularisation
Description
Freedom from clinical driven target lesion revascularization defined as absence of any reintervention due to clinical deterioration, defined as a worsening of the patient's quality of life, reflected by the health-questionnaire (EQ-5D), worsening of the Rutherford category with minimal 1 class or worsening of wound status.
Time Frame
6 and 12 months post-procedure
Title
Amputation free survival
Description
Amputation free survival defined as alive with freedom from any above the ankle target limb amputation
Time Frame
6 and 12 months post-procedure
Title
Limb salvage
Description
Limb salvage is defined as freedom from any above the ankle target limb amputation
Time Frame
6 and 12 months post-procedure
Title
Procedural success
Description
Procedural success is defined as restoration of at least 1 below the knee artery with <30% residual stenosis in the final angiogram and outflow into the foot.
Time Frame
During index procedure
Title
Wound healing status
Description
Wound healing status is based on three parameters: the wound's diameter, the wound's depth and the % granulation tissue. These three parameters will be aggregated to one reported value using the modified Strauss wound classification scoring system.
Score 2: >75% red granulation tissue / <1cm² wound size / wound depth to the skin or subcutaneous.
Score 1: 50-75% red granulation tissue / 1-9cm² wound size / wound depth to muscle or tendon.
Score 0: <50% red granulation tissue / >9cm² wound size / wound depth to the bone or joint
Time Frame
1, 6 and 12 months post-procedure
Title
Wound healing time
Description
Wound healing time is defined as the number of days needed for the wound to heal completely after the index procedure.
Time Frame
1, 6 and 12 months post-procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or non-pregnant females ≥ 18 years of age at the time of consent. Females 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 participants will be exempted from this requirement in case they are sterile, infertile or have been post-menopausal for at least 12 months
Subject has been informed of and understands the nature of the study and provides signed informed consent to participate in the study. If the subject possesses the ability to understand and provide informed consent but due to physical inability, the subject cannot sign the informed consent form. An impartial witness may sign on behalf of the subject.
Willing to comply with all required follow-up visits
Rutherford Classification 5
Significant degree of stenosis >70% or chronic total occlusion (CTO)
Infrapopliteal lesion: P3 to the ankle-joint level (not below-the-ankle (BTA)); full length lesions or tandem lesions are allowed
Wound, Ischemia, foot Infection (WIfI) tissue loss grade 1-2 at baseline
WIfI foot infection grade of 0-2 at baseline
WIfI ischemia grade 2-3 at baseline
Estimated life expectancy ≥ 1 year
Multiple lesions can be treated if they are located in separate vessels per standard of care but only one (1) BTK vessel can be considered as the target lesion/vessel and need to be treated according the Clinical Investigation Protocol (CIP) guidelines.
Target vessel should give direct or indirect run-off to the foot (clearly documented in a foot/BTA angiogram)
Patients with in-flow lesions can be included if the lesions are treated successfully (residual stenosis ≤30%) with the same drug coated balloon (DCB) platform, bail-out stenting with a bare-metal stent (BMS).
Successful pre-dilatation of the target lesion (≤30% residual stenosis)
Exclusion Criteria:
Previous bypass graft in the target limb
Acute limb ischemia, defined as symptom onset during less than 14 days prior to the index procedure
Prior or planned above-the-ankle amputation to the target limb (this does not apply to ray amputation of ≤2 digits, simple digital amputations or ulcer debridement)
Previous DCB treatment in target vessel 6 months prior to index procedure
WIfI tissue loss grade 0 or 3 at baseline
WIfI foot infection grade 3 at baseline
WIfI ischemia grade 0-1 at baseline
Any systemic infection or immunocompromised state. Patients with an ascending infection/deep foot infection or abscess/white blood count (WBC)≥12.000/or febrile state or C reactive protein (CRP)>5mg/L
Endovascular or surgical procedure (not including diagnostic procedures, planned simple digital amputation or wound debridement) to the target limb within 30 days after the index procedure
Existing stent implant in the target vessel
Use of alternative therapies: atherectomy, cutting/scoring balloons, laser, …
Known coagulopathy, hypercoagulable state, bleeding diathesis, other blood disorder, or a platelet count less than 80.000/μL or greater than 500.000/μL
Any subject in which antiplatelet, anticoagulant or thrombolytic therapy is contraindicated
Myocardial infarction, coronary thrombolysis or angina less than 30 days prior to the index procedure
History of stroke or transient ischemic attack (TIA) less than 90 days prior to the index procedure
Known hypersensitivity or contraindication to nickel-titanium alloy (Nitinol)
Has other comorbidities that, in the opinion of the investigator, would preclude them from receiving this treatment and/or participating in study-required follow-up
Patients on haemodialysis
Known hypersensitivity or allergy to contrast agents that cannot be medically managed
Known hypersensitivity or allergy to heparin, aspirin, paclitaxel, clopidogrel or other antiplatelet/anticoagulant therapies
Inadequate inflow lesion treatment (>30% residual stenosis)
Inadequate result of pre-dilatation (>30% residual stenosis)
Inadequate run-off to the foot
Bilateral BTK enrolment in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Koen Deloose, MD
Organizational Affiliation
ID3 Medical
Official's Role
Study Director
Facility Information:
Facility Name
OLV Ziekenhuis Aalst
City
Aalst
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Imelda Hospital
City
Bonheiden
ZIP/Postal Code
2820
Country
Belgium
Facility Name
A.Z. Sint-Blasius
City
Dendermonde
ZIP/Postal Code
9200
Country
Belgium
Facility Name
Z.O.L.
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Facility Name
AZ Groeninge
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Regionaal Ziekenhuis Heilig Hart
City
Tienen
ZIP/Postal Code
3300
Country
Belgium
Facility Name
Policlinico Abano Terme
City
Abano Terme
State/Province
Padua
ZIP/Postal Code
1-35031
Country
Italy
Facility Name
IRCCS Policlinico San Donato
City
San Donato
ZIP/Postal Code
20097
Country
Italy
Facility Name
Hospital Univ. Germans Trias I Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Belgian-Italian Trial to Evaluate the Efficacy and Safety of Below The Knee (BTK) Treatment With the Luminor 14 Paclitaxel Coated Percutaneous Transluminal Angioplasty Balloon Catheter of iVascular
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