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
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: ID3 Medical

NCT03845543 
Date 29-JULY-2019 
 
 
BIBLIOS-study 
 
CIP v1.1 
29-JULY-2019 
 1/5 
 
BIBLIOS STUDY: SYNOPSIS 
Title 
BIBLIOS-study: 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 
Objective 
The objective of this clinical investigation is to access the safety and efficacy of the 
Luminor-14 DCB for the treatment of infrapopliteal lesions in 150 subjects with 
critical limb ischemia 
Methodology 
Prospective, single-arm, multicentre, physician initiated clinical study 
Enrolment 
150 subjects 
Primary 
Endpoint 
1. Efficacy endpoint – Freedom from MALE at 6 months 
Freedom from major adverse limb events (MALE) at 6 months 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). 
 
2. Safety endpoint – Freedom from MALE or POD at 30 days 
Freedom from major adverse limb events (MALE) at 30 days defined as absence 
of above-the-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) 
 
Peri-operative death (POD) at 30 days, device or procedure related or any other 
cause. 
Secondary 
Endpoint 
1. Target Vessel Functional Flow Assessment at 6 and 12 months 
Target vessel functional flow assessment at 6 and 12 months defined as the 
presence of blood flow using duplex ultrasound. If angiography is available within 
the 12-month follow-up visit window, it should be used instead of the duplex 
ultrasound. Evidence of no blood flow within the treated segment indicates loss 
of patency. 
 
2. Freedom from CD-TLR at 6 and 12 months 
Freedom from clinical driven target lesion revascularization (CD-TLR) at 6 and 12 
months defined as absence of any reintervention due to clinical deterioration, 
defined as a worsening of the patient’s quality of life, reflected by the EQ5D-
questionnaire, worsening of the Rutherford category with minimal 1 class or 
worsening of wound status 
 
3. Amputation free survival at 6 and 12 months 
Amputation free survival defined as alive with freedom from any above-the-ankle 
target limb amputation 
 
4. Limb salvage at 6 and 12 months 
Limb salvage is defined as freedom from any above-the-ankle target limb 
amputation at 6 and 12 months 
 

NCT03845543 
Date 29-JULY-2019 
 
 
BIBLIOS-study 
 
CIP v1.1 
29-JULY-2019 
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5. Procedural success 
Procedural success is defined as restoration of at least 1 below-the-knee (BTK) 
artery with <30% residual stenosis in the final angiogram and outflow into the 
foot 
 
6. Wound healing status 
Wound healing status is based on three parameters: the wound’s diameter, the 
wound’s depth and the % granulation tissue. 
 
7. Wound healing time 
Wound healing time is defined as the number of days needed for the wound to 
heal completely after the index procedure 
Inclusion 
criteria 
1. 
Males or non-pregnant females g 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 
2. 
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. 
3. 
Willing to comply with all required follow-up visits 
4. 
Rutherford Classification 5 
5. 
Significant degree of stenosis >70% or chronic total occlusion (CTO) 
6. 
Infrapopliteal lesion: P3 to the ankle-joint level (not below-the-ankle (BTA)); full 
length lesions or tandem lesions are allowed 
7. 
WIfI tissue loss grade 1-2 at baseline 
8. 
WIfI foot infection grade of 0-2 at baseline 
9. 
WIfI ischemia grade 2-3 at baseline 
10. Estimated life expectancy g 1 year 
11. 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 CIP guidelines 
12. Target vessel should give direct or indirect run-off to the foot (clearly 
documented in a foot/BTA angiogram) 
13. Patients with in-flow lesions can be included if the lesions are treated 
successfully (residual stenosis f30%) with the same drug coated balloon (DCB) 
platform, bail-out stenting with a bare-metal stent (BMS) 
14. Successful pre-dilatation of the target lesion (f30% residual stenosis) 
Exclusion 
Criteria 
1. 
Previous bypass graft in the target limb 
2. 
Acute limb ischemia, defined as symptom onset during less than 14 days prior to 
the index procedure 
3. 
Prior or planned above-the-ankle amputation to the target limb (this does not 
apply to ray amputation of f2 digits, simple digital amputations or ulcer 
debridement) 
4. 
Previous DCB treatment in target vessel 6 months prior to index procedure 
5. 
WIfI tissue loss grade 0 or 3 at baseline 
6. 
WIfI foot infection grade 3 at baseline 
7. 
WIfI ischemia grade 0-1 at baseline 

NCT03845543 
Date 29-JULY-2019 
 
 
BIBLIOS-study 
 
CIP v1.1 
29-JULY-2019 
 3/5 
8. 
Any systemic infection or immunocompromised state. Patients with an 
ascending infection/deep foot infection or abscess/white blood count 
(WBC)g12.000/or febrile state or CRP>5mg/L 
9. 
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 
10. Existing stent implant in the target vessel 
11. Use of alternative therapies: atherectomy, cutting/scoring balloons, laser, & 
12. Known coagulopathy, hypercoagulable state, bleeding diathesis, other blood 
disorder, or a platelet count less than 80.000/µL or greater than 500.000/µL 
13. Any subject in which antiplatelet, anticoagulant or thrombolytic therapy is 
contraindicated 
14. Myocardial infarction, coronary thrombolysis or angina less than 30 days prior to 
the index procedure 
15. History of stroke or transient ischemic attack (TIA) less than 90 days prior to the 
index procedure 
16. Known hypersensitivity or contraindication to nickel-titanium alloy (Nitinol) 
17. 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 
18. Patients on haemodialysis 
19. Known hypersensitivity or allergy to contrast agents that cannot be medically 
managed 
20. Known hypersensitivity or allergy to heparin, aspirin, paclitaxel, clopidogrel or 
other antiplatelet/anticoagulant therapies 
21. Inadequate inflow lesion treatment (>30% residual stenosis) 
22. Inadequate result of pre-dilatation (>30% residual stenosis) 
23. Inadequate run-off to the foot 
24. Bilateral BTK enrolment in this study 
P.I. 
Dr. Koen Deloose, A.Z. Sint-Blasius, Dendermonde, Belgium 
 
Study conduct 
The study will be conducted in accordance with the Declaration of Helsinki and ISO 
14155:2011 and comply with requirements regarding Ethics Committees and any 
other applicable regulations. 
 
 
 
 
 
 
 
 
 
 
 
 

NCT03845543 
Date 29-JULY-2019 
 
 
BIBLIOS-study 
 
CIP v1.1 
29-JULY-2019 
 4/5 
Study 
investigations 
Time  
 
Tests and Procedures 
Pre-Procedure 
(up to 24 hours before procedure, 
unless otherwise noted) 
1. 
2. 
3. 
4. 
5. 
6. 
7. 
Screening inclusion/exclusion criteria 
Consenting patient 
Physical exam (ABI, Rutherford) 
WIfI assessment 
Medical History 
Medication Registration 
EQ5D-questionnaire 
Procedure 
1. 
2. 
3. 
4. 
Angiographic inclusion/exclusion criteria 
Study inclusion 
Intervention details 
Adverse Event recording/reporting  
Pre-Discharge  
1. 
2. 
3. 
4. 
5. 
6. 
Medication Registration 
Physical Examination (ABI, Rutherford) 
WIfI assessment 
Wound healing status 
EQ5D-questionnaire 
Adverse Event recording/reporting 
Weekly follow-up by a dedicated 
wound care specialist until the 
wound is healed (does not need to 
be in the hospital) 
1. 
2. 
Wound healing status 
Picture with ruler 
1-month Follow-up  
( 14 days) 
1. 
2. 
3. 
4. 
5. 
6. 
 
7. 
Medication Registration 
Physical Examination (ABI, Rutherford) 
WIfI assessment 
Wound healing status 
EQ5D-questionnaire 
Target vessel functional flow assessment 
on color flow doppler ultrasound 
Adverse Event recording/reporting 
6-month Follow-up  
( 30 days) 
1. 
2. 
3. 
4. 
5. 
6. 
 
7. 
Medication Registration 
Physical Examination (ABI, Rutherford) 
WIfI assessment 
Wound healing status 
EQ5D-questionnaire 
Target vessel functional flow assessment 
on color flow doppler ultrasound 
Adverse Event recording/reporting 
 12-month Follow-up  
( 30 days) 
1. 
2. 
3. 
4. 
5. 
6. 
 
7. 
Medication Registration 
Physical Examination (ABI, Rutherford) 
WIfI assessment 
Wound healing status 
EQ5D-questionnaire 
Target vessel functional flow assessment 
on color flow doppler ultrasound 
Adverse Event recording/reporting 
 
 
 
 
 

NCT03845543 
Date 29-JULY-2019 
 
 
BIBLIOS-study 
 
CIP v1.1 
29-JULY-2019 
 5/5 
 Statistical Analysis Plan (SAP)  
 
 
 
Descriptive data summaries will be used to present and summarize the collected data. For 
categorical variables (e.g. Gender) frequency distributions and cross tabulations will be given. 
For numeric variables (e.g. Patient age) minimum, maximum, mean, median and standard 
deviation will be calculated. For all variables a 95% confidence interval for the relevant 
parameters of the underlying distribution will be calculated. For all time-dependent events 
life-tables will be calculated using the Kaplan Meier estimate method, for a period starting on 
the date of the procedure up to and including the 12-month follow-up visit. Stratification to 
pre-procedural risk factors, Rutherford-, WIfI-classifications and lesion criteria will be 
performed and the log rank test will be used to compare between the different outcomes, 
associated p-values < 0.05 are defined as significant.