Lutonix DCB Versus Standard Balloon Angioplasty for Treatment of Below-The-Knee (BTK) Arteries

Study Overview
=================
Brief Summary
-----------------
To assess the safety and efficacy of the Lutonix Drug Coated Balloon (DCB) for treatment of stenosis or occlusion of native below-the-knee arteries.

Official Title
-----------------
A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial Comparing the Lutonix Drug Coated Balloon Versus Standard Balloon Angioplasty for Treatment of Below-the-Knee (BTK) Arteries(Lutonix BTK Trial)

Conditions
-----------------
Critical Limb Ischemia

Intervention / Treatment
-----------------
* Device: Lutonix DCB
* Device: Uncoated PTA Catheter


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or non-pregnant female ≥18 years of age; Rutherford Clinical Category 3, 4 & 5; Life expectancy ≥ 1 year; Significant stenosis (≥70%) A patent inflow artery; Target vessel(s) diameter between 2 and 4 mm; Target vessel(s) reconstitute(s) at or above the ankle Exclusion Criteria: Pregnant or planning on becoming pregnant; History of stroke within 3 months; History of MI, thrombolysis or angina within 30 days of enrollment; Planned major amputation (of either leg) Prior major amputation if amputation occurred less than one year prior to enrollment and if patient is not independently ambulating; GFR ≤ 30 ml/min per 1.73m2; Acute limb ischemia; In-stent restenosis of target lesion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lutonix DCB<br>Lutonix Paclitaxel Drug Coated Balloon | Device: Lutonix DCB<br> <br> * Other names: LTX DCB;|
| Active Comparator: PTA Catheter<br>Standard Uncoated PTA Catheter | Device: Uncoated PTA Catheter<br> <br> * Other names: PTA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Freedom From Below-the-Knee (BTK) Major Adverse Limb Event and Peri-Operative Death (POD) at 30 Days Post Index Procedure. | The primary safety endpoint is defined as freedom from the composite of all-cause death, above-ankle amputation or major reintervention (new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis) of the index limb involving a below-the-knee artery. | 30 days post index procedure | 
| Number of Participants With Freedom From the Composite of Above-ankle Amputation, Target Lesion Occlusion, and Clinically-driven Target Lesion Revascularization at 6 Months Post Index Procedure. | The primary efficacy endpoint is defined as freedom from the composite of above-ankle amputation, target lesion occlusion, and clinically-driven target lesion revascularization. All amputations included in endpoints refer to amputations in the index limb. | 6 months post-index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Lesions Considered Technical Success at Time of Index Procedure | Technical Success: A success is determined if the device success was achieved and a final residual stenosis post study device (DCB or placebo) dilatation ≤ 30% was reported. | At time of index procedure | 
| Percentage of Procedures With Procedural Success at Time of Index Procedure. | A success is determined if there is restoration of at least 1 infrapopliteal artery with residual stenosis ≤ 30% (or ≤ 50% depending upon the version of the protocol) and inline outflow to the foot, irrespective of device success, and without a major adverse event during the index procedure. | At time of Index Procedure | 
| Comparison of the Below the Knee (BTK) Major Adverse Limb Event (MALE) and Perioperative Death (POD) Rate to a Performance Goal at 30 Days Post Index Procedure. |  | 30 days post index procedure | 
| Change in European Quality of Life 5 Dimensions (EuroQol -5D) Scores at 30 Days, 6 and 12 Months Compared to Baseline. | Mean change in EuroQol (EQ-5D) scores at 30 days, 6, and 12 months compared to baseline. The EurolQol-5D system rates quality of life using five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of ratings, that is, no problems, slight problems, moderate problems, severe problems and extreme problems that can be selected. A visual scale allows participants to report their own perception of their health status. The overall scores range from 0 (worst) to 100 (best). Please note that the data in the table below represent the mean changes in overall scores for each group compared to their baseline data. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure compared to baseline | 
| Late Lumen Loss at 12 Months Post Index Procedure |  | 12 months post-index procedure | 
| Number of Healed Wounds at 30 Days, 6 and 12 Months Post Index Procedure | Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. The number of wounds analyzed at 6 and 12 months post-index procedure includes wounds that may have appeared (new wounds) since the previous time period reporting. | 30 days, 6 and 12 months post index procedure | 
| Number of Non-Healed Wounds by Category (Improving, Stagnant and Worsening) at 30 Days, 6 and 12 Months Post-Index Procedure. |  | 30 days, 6 and 12 months post index procedure | 
| Percentage of Existing, New, and Recurrent Wounds at 30 Days, 6 and 12 Months Post Index Procedure. | Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Change in Rutherford Classification Scores at 30 Days, 6 and 12 Months Post Index Procedure Compared to Baseline. | The endpoint summarizes the change in index-limb Rutherford Classification of participants from baseline through 36 months. Data is presented as shift from baseline Rutherford Classification data using the following categories: 1) Improvement, 2) Same, and 3) Worsened. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure compared to baseline | 
| Number of Participants With Freedom From Above Ankle Amputation, Unhealed Wound, Ischemic Rest Pain, Target Vessel Occlusion, and Clinically-Driven Target Vessel Revascularization (TVR) at 30 Days, 6 and 12 Months Post Index Procedure. | The composite endpoint of freedom from above ankle amputation (CEC-adjudicated), unhealed wound (presence of wound vs. no wound), ischemic rest pain (Rutherford category 4 or higher), target vessel occlusion (based on DUS and/or angiograph), and clinically-driven TVR (CEC-adjudicated). Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Percentage of Participants With Freedom From Primary Patency Failure at 30 Days, 6 and 12 Months Post Index Procedure | Primary patency is defined as the absence of both total occlusion (100% diameter stenosis) in all of the target lesions in a flow pathway as well as a clinically-driven Target Lesion Revascularization (TLR). Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days and at 6 and 12 months | 
| Percentage of Lesions With Primary Patency Excluding Early Mechanical Recoil at 30 Days, 6 and 12 Months Post Index Procedure | Primary patency with exclusion of early mechanical recoil of the target flow pathway is defined as the absence of both total occlusion (100% diameter stenosis) of the target lesions and clinically-driven TLR events > 30 days. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Number of Lesions With Secondary Patency at 30 Days, 6 and 12 Months Post Index Procedure | The secondary patency of the target lesion is defined as the absence of total occlusion (100% diameter stenosis) of the target lesions based on angiography (if performed) or ultrasound as analyzed by the angiographic Core Lab. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Composite of Freedom From Clinically -Driven Target Lesion Revascularization (TLR) and From 50% DS by Angiography or Duplex Ultrasound at 30 Days, 6 and 12 Months Post Index Procedure. |  | 30 days, 6 and 12 months post index procedure | 
| Change in Toe Brachial Index (TBI) at 30 Days, 6 and 12 Months Post Index Procedure Compared to Baseline | Mean change from baseline values. The Toe Brachial Index (TBI) is defined as a ratio of toe to brachial (upper arm) artery systolic blood pressure and aims at determining how well the blood is flowing in the legs. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure compared to baseline | 
| Change in Ankle Brachial Index (ABI) at 30 Days, 6 and 12 Months Post Index Procedure Compared to Baseline | Mean change from baseline values. The Ankle Brachial Index (ABI) is defined as a ratio of ankle to brachial (upper arm) artery systolic blood pressure and aims at determining how well the blood is flowing in the legs. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, and at 6 and 12 months compared to baseline | 
| Change in Walking Impairment Questionnaire (WIQ) Scores at 30 Days, 6 and 12 Months Post Index Procedure Compared to Baseline. | The WIQ assesses 3 categories of activities that include 1) walking distance, 2) stair-climbing, and 3) walking speed. Each question requires participants to rate their degree of difficulty with the activity on a scale of 0 (unable) to 4 (no problem). Final scores range from 0% to 100%, with lower percentages indicating higher levels of difficulties with activities.The results below represent the mean differences in total Walking Impairment Questionnaire (WIQ) scores at 30 days 6 and 12 months, compared to baseline assessment scores. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure compared to baseline | 
| Number of Participants With Clinically-Driven Target Lesion Revascularization (TLR) at 30 Days, 6 and 12 Months Post Index Procedure |  | 30 days, 6 and 12 months post index procedure | 
| Cumulative Number of Target Lesion Revascularization (TLR) at 30 Days, 6 and 12 Months Post Index Procedure. | Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Number of Participants With Clinically-Driven Target Vessel Revascularization (TVR) at 30 Days, 6 and 12 Months Post Index Procedure. |  | 30 days, 6 and 12 months post index procedure | 
| Cumulative Number of Target Vessel Revascularization (TVR) at 30 Days, 6 and 12 Months Post Index Procedure. |  | 30 days, 6 and 12 months post index procedure | 
| Percentage of Participants With Freedom From Limb Amputation at 30 Days, 6 and 12 Months Post Index Procedure | Limb salvage defined as no amputation of target limb. | 30 days and at 6 and 12 months | 
| Percentage of Participants With Freedom From Unplanned Below the Knee (BTK) Amputation of the Target Limb at 30 Days, 6 and 12 Months Post Index Procedure. | Defined as amputation that was below the ankle, including digit amputation. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Cumulative Number of of Below the Knee (BTK) Index-Limb Reinterventions at 30 Days, 6 and 12 Months Post Index Procedure. | The overall burden of BTK reinterventions was defined as the total number of BTK index-limb re-interventions and major amputations for each time point. Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure | 
| Percentage of Participants With Freedom From Composite of Perioperative Death (POD), Index Limb-related Death, Below the Knee Reinterventions or Major Amputations of the Index Limb at 30 Days, 6 and 12 Months Post Index Procedure | Results for 24 and 36 months will be reported when the final Clinical Study Report becomes available. | 30 days, 6 and 12 months post index procedure |