DiRectional AthErectomy + Drug CoAted BaLloon to Treat Long, CalcifIed FemoropopliTeal ArterY Lesions

Study Overview
=================
Brief Summary
-----------------
This study is designed to collect information during a procedure that is routine care for treating a blockage in a blood vessel in the upper part of the participant's leg. This study is for data collection reasons to help doctors gain better understanding of the treatment of disease in the blood vessels of the legs. You will be treated with two devices that are routine, or standard of care, for your doctor to treat blockages in the blood vessel of the leg. The treatment is for a blockage or narrowing caused by plaque build-up in the blood vessel. Data will be collected to assess what length of time the blood vessel will be prevented from re-narrowing through twenty-four (24) months after the procedure.

Detailed Description
-----------------
This prospective study will evaluate the safety and effectiveness of two FDA 510(k) cleared DA products (Medtronic HawkOne® and TurboHawkM)19-21 and FDA approved drug-coated balloon (Medtronic IN.PACT® Admiral®)22 used in combination to debulk moderate and severely calcified femoropopliteal artery atherosclerotic lesions as defined by the published Peripheral Arterial Calcium Scoring System (PACSS) followed by treatment with the Medtronic IN.PACT® Admiral® DCB for the prevention of restenosis as assessed at 12-month follow-up. The data will be independently adjudicated by an angiographic and DUS core labs. An independent IVUS core lab to determine change in maximal luminal plaque area, pre- and post-atherectomy and post-adjunctive DCB therapy will adjudicate the assessment of debulking effectiveness. The operator will be blinded to all IVUS images and procedural success will be based on usual and customary angiographic visual assessments. The post-atherectomy plaque debulking effectiveness (change in plaque area) and vascular calcium severity as assessed by IVUS will be correlated with the angiographic metrics of RVD, pre- and post-treatment MLD, calcium grade (using PACSS), lesion length, sub-intimal wire passage, CTO length, and angiographic patterns of restenosis in all patients who sustain a CD-TLR through 12-months. All atherectomy specimens will be collected and provided to an independent histology laboratory for analysis of calcium content and vessel wall elements. The amount of embolic debris captured in the Spider® Distal Protection Device will be visually assessed. The study will validate PACSS definitions of moderate and severe calcium and its location (intimal, medial or mixed) as they relate to intra-procedural and Major Adverse Events (MAEs) through 30-day clinical follow-up (e.g., grade D-F dissections requiring provisional stenting, vessel perforation requiring an additional intervention or surgery, vessel thrombosis requiring adjunctive technologies and/or lytic agents, unplanned amputation, intra-procedure distal embolization, and CD-TLR).

Official Title
-----------------
The REALITY Study: DiRectional AthErectomy + Drug-CoAted BaLloon to Treat Long, CalcifIed FemoropopliTeal ArterY Lesions

Conditions
-----------------
Peripheral Vascular Disease

Intervention / Treatment
-----------------
* Device: Medtronic HawkOne® or TurboHawk™
* Device: Medtronic IN.PACT® Admiral® DCB
* Device: Medtronic Spider™ Distal Protection Device (DPD)
* Device: Volcano Visions® PV .014 IVUS catheter
* Device: Nitinol Stent Placement


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: General Inclusion Criteria: Willing and able to provide informed consent; Age ≥ 18 years of age; Clinical evaluation determines Rutherford Category 2-4; Willing to comply with all study requirements; All lab work is within acceptable limits to undergo a percutaneous interventional procedure. Life expectancy, in the investigator's opinion, of at least 24 months. Angiographic Inclusion Criteria: RVD ≥ 4mm and ≤ 7mm; Evidence of a ≥70% de novo or restenotic lesion or occlusion in the target lesion defined as in the superficial femoral artery and/or popliteal artery, located in the arterial segment starting at least 1 cm beyond the Common Femoral Artery (CFA) bifurcation between the superficial and profunda femoris arteries (proximal anatomical landmark) to the distal P2 segment of the popliteal artery; Total lesion/occlusion length: a. ≥ 8 cm and ≤ 18 cm Total occlusion length a. ≥ 6 cm and ≤10 cm Stenosis or occlusion begins 1cm below the profunda-SFA bifurcation; Femoral or popliteal stenosis or occlusion that does not extend beyond the P2 popliteal segment; Minimum 1 patent infrapopliteal vessel to the foot with ≤ 50% diameter stenosis; Grade 3 or 4 intimal, medial and/or mixed calcification per the PACSS as judged by the operator at the time of the procedure; Index lesion fits within guidelines below: 9.1 If two lesions are ≤ 3 cm apart, treatment would be allowed as a single lesion providing they contain a segment of moderate or severe calcification and the total lesion length is ≥ 8 cm and ≤18 cm. 9.2 If more than one lesion is within the target vessel, and they are separated by > 3 cm of normal vessel, one lesion must be designated by the investigator as the target lesion as long as the lesion meets all angiographic eligibility criteria. Only one index lesion is permitted for analysis, but study will allow a second lesion to be treated as a non-target lesion. Infrapopliteal lesion, if diagnosed, can be staged and treated > 30 days after index procedure. Exclusion Criteria: General Exclusion Criteria: Renal failure or chronic kidney disease with GFR ≤30 ml/min or MDRD GFR ≤30 ml/min per 1.73m2 (and serum creatinine ≥2.5 mg/dL within 30 days of index procedure); Physician does not believe subject is an appropriate candidate for study; Previous infra-inguinal intervention in the index limb within 30 days of the planned femoropopliteal intervention Angiographic Exclusion Criteria: Inability to cross lesion/occlusion with a guidewire or re-entry device; Inability for the guidewire to re-enter and/or remain in the true lumen prior to enrollment; In-stent restenosis of the target lesion, or recognition of any stent (patent or re-stenotic within the femoropopliteal segment of the index limb; Aneurysm located in the target vessel or aneurysmal vessel; Acute thrombus in the index limb prior to enrollment.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Non-randomized<br>Directional Atherectomy + Drug Coated Balloon: DA followed by DCB will be performed in all enrolled subjects. DA includes the use of Intervention 'Medtronic HawkOne® or TurboHawk™. Medtronic Spider™ Distal Protection Device (DPD) is recommended for use according to IFU. Medtronic IN.PACT® Admiral® DCB will be used after DA. Volcano Visions® PV .014 IVUS catheter required to assess lesion in each procedure. Nitinol Stent Placement: Only FDA approved nitinol stents can be used if provisional stenting is required. | Device: Medtronic HawkOne® or TurboHawk™<br>* Use of FDA Cleared Directional Atherectomy (DA) Devices. Medtronic HawkOne® Directional Atherectomy System or TurboHawk™ Plaque Excision System. DA followed by DCB will be performed in all enrolled subjects.<br>Device: Medtronic IN.PACT® Admiral® DCB<br>* FDA Approved Drug Coated Balloon (DCB) Technology. Medtronic IN.PACT® Admiral® DCB will be used after DA.<br>Device: Medtronic Spider™ Distal Protection Device (DPD)<br>* It is recommended that the Medtronic Spider™ Distal protection device (DPD) be paired with DA when used in complex, calcified lesions (TurboHawk™ IFU).<br>Device: Volcano Visions® PV .014 IVUS catheter<br>* Lesion IVUS assessment using the Volcano Visions® PV .014 IVUS catheter will be required in all cases.<br>Device: Nitinol Stent Placement<br>* Only FDA approved nitinol stents can be used if provisional stenting is required.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency | One-year primary patency (PSVR ≤2.4) and freedom from CD-TLR in subjects with long, moderate and severely calcified symptomatic femoropopliteal arterial stenoses and occlusions after treatment with DA+DCB. | One year | 
| Freedom from MAE | Freedom from (MAEs) defined as freedom from flow-limiting dissections (D-F), vessel perforations, unplanned amputation, intra-procedure distal athero-embolization and clinically-driven TVR in subjects with long, moderate and severely calcified femoropopliteal lesions and occlusions through 30 day follow up. | One month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success | Device Success: ≤ 30% residual stenosis after completion of directional atherectomy procedure (stand-alone) as assessed by the angiographic core lab. | Post Index Procedure | 
| Procedural Success | Procedural Success: ≤30% residual stenosis after completion of the directional atherectomy procedure and DCB as assessed by the angiographic core lab. | Post Index Procedure | 
| IVUS | Core lab assessed correlation between IVUS metrics of luminal diameter, change in plaque area and luminal gain pre- and post-atherectomy, and angiographic core lab assessment of pre- and post-percent diameter stenosis (%DS) and the extent of vascular calcification will be determined | Post Index Procedure | 
| PACCS scoring and related procedural complications | The association of moderate and severe calcification as defined by the Peripheral Arterial Calcium Scoring System (PACSS) and the change in %DS, procedure related complications (residual stenosis ≥50%, vessel recoil and/or high-grade dissections requiring use of adjunct technologies) visual quantification of embolic material in the distal protection device and MAEs through 30-days will be assessed | 1 month | 
| Directional Atherectomy | Directional Atherectomy device specific metrics of total directional atherectomy time as a function of lesion length, lesion morphology, and total procedure time. | Post Index Procedure | 
| Major Adverse Events thru 24 months | Major adverse events through 24-months defined as composite clinically-driven target lesion revascularization (CD-TVR) defined as any re-intervention within the target vessel due to symptoms associated with a drop from post-intervention ABI/TBI >20% or >0.15, major unplanned amputation of the treated limb, and all-cause mortality post 30 day follow up through 2 year follow up. | 24 months | 
| Post procedure TVR | TVR within 6, 12, 24 months post index procedure | 6, 12, 24 months | 
| CD-TLR post procedure | TLR within 6, 12, 24 months post index procedure | 6, 12, 24 months | 
| Time to CD-TLR thru 24 months post procedure | Time to first clinically-driven target lesion revascularization (TLR) through 24 months post-index procedure | 24 months | 
| Major target limb amputation post procedure | Major target limb amputation within 6, 12, 24 months post index procedure | 6, 12, 24 months | 
| Thrombosis- target lesion post procedure | Thrombosis at the target lesion site within 6, 12, 24 months post index procedure | 6, 12, 24 months | 
| Primary sustained clinical improvement | Primary sustained clinical improvement: An improvement shift in the Rutherford classification of at least one class in amputation- and TVR-free surviving subjects at 6, 12, 24 months post procedure | 6, 12, 24 months | 
| Secondary sustained clinical improvement | Secondary sustained clinical improvement: An improvement shift in the Rutherford classification of at least one class including the need for clinically-driven TVR in amputation-free surviving subjects at 6, 12, 24 months post index procedure | 6, 12, 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atherectomy, Drug-Coated Balloon