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

Peripheral Vascular Disease Clinical Trial

— REALITY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02850107
• Other study ID #: VIVA-CLIN-2016-01
• Status: Completed
• Phase: N/A
• Start date: June 1, 2016
• Est. completion date: June 16, 2020

Study information

• Verified date: October 2020
• Source: VIVA Physicians
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: June 16, 2020
• Est. primary completion date: June 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

General Inclusion Criteria:

1. Willing and able to provide informed consent;

2. Age = 18 years of age;

3. Clinical evaluation determines Rutherford Category 2-4;

4. Willing to comply with all study requirements;

5. All lab work is within acceptable limits to undergo a percutaneous interventional procedure.

6. Life expectancy, in the investigator's opinion, of at least 24 months.

Angiographic Inclusion Criteria:

1. RVD = 4mm and = 7mm;

2. 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;

3. Total lesion/occlusion length:

a. = 8 cm and = 18 cm

4. Total occlusion length

a. = 6 cm and =10 cm

5. Stenosis or occlusion begins 1cm below the profunda-SFA bifurcation;

6. Femoral or popliteal stenosis or occlusion that does not extend beyond the P2 popliteal segment;

7. Minimum 1 patent infrapopliteal vessel to the foot with = 50% diameter stenosis;

8. Grade 3 or 4 intimal, medial and/or mixed calcification per the PACSS as judged by the operator at the time of the procedure;

9. 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.

10. Infrapopliteal lesion, if diagnosed, can be staged and treated > 30 days after index procedure.

Exclusion Criteria:

General Exclusion Criteria:

1. 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);

2. Physician does not believe subject is an appropriate candidate for study;

3. Previous infra-inguinal intervention in the index limb within 30 days of the planned femoropopliteal intervention

Angiographic Exclusion Criteria:

1. Inability to cross lesion/occlusion with a guidewire or re-entry device;

2. Inability for the guidewire to re-enter and/or remain in the true lumen prior to enrollment;

3. In-stent restenosis of the target lesion, or recognition of any stent (patent or re-stenotic within the femoropopliteal segment of the index limb;

4. Aneurysm located in the target vessel or aneurysmal vessel;

5. Acute thrombus in the index limb prior to enrollment.

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

Device:
• Medtronic HawkOne® or TurboHawk™
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.
• Medtronic IN.PACT® Admiral® DCB
FDA Approved Drug Coated Balloon (DCB) Technology. Medtronic IN.PACT® Admiral® DCB will be used after DA.
• Medtronic Spider™ Distal Protection Device (DPD)
It is recommended that the Medtronic Spider™ Distal protection device (DPD) be paired with DA when used in complex, calcified lesions (TurboHawk™ IFU).
• Volcano Visions® PV .014" IVUS catheter
Lesion IVUS assessment using the Volcano Visions® PV .014" IVUS catheter will be required in all cases.
• Nitinol Stent Placement
Only FDA approved nitinol stents can be used if provisional stenting is required.

Locations

Country	Name	City	State
United States	Austin Heart	Austin	Texas
United States	St. Elizabeth's	Boston	Massachusetts
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	University of Mississippi	Jackson	Mississippi
United States	Longview Cardiac and Vascular Consultants	Longview	Texas
United States	Mount Sinai	New York	New York
United States	Rex	Raleigh	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
VIVA Physicians	Medtronic

Country where clinical trial is conducted

United States, 

References & Publications (17)

Cioppa A, Stabile E, Popusoi G, Salemme L, Cota L, Pucciarelli A, Ambrosini V, Sorropago G, Tesorio T, Agresta A, Biamino G, Rubino P. Combined treatment of heavy calcified femoro-popliteal lesions using directional atherectomy and a paclitaxel coated bal — View Citation

Fanelli F, Cannavale A, Gazzetti M, Lucatelli P, Wlderk A, Cirelli C, d'Adamo A, Salvatori FM. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease. Cardiovasc Intervent Radiol. 2014 Aug;37(4):898-907. doi: 10.1007/ — View Citation

Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006 Aug 15;114(7):688-99. Review. — View Citation

Goodney PP, Travis LL, Nallamothu BK, Holman K, Suckow B, Henke PK, Lucas FL, Goodman DC, Birkmeyer JD, Fisher ES. Variation in the use of lower extremity vascular procedures for critical limb ischemia. Circ Cardiovasc Qual Outcomes. 2012 Jan;5(1):94-102. — View Citation

Laird JR, Schneider PA, Tepe G, Brodmann M, Zeller T, Metzger C, Krishnan P, Scheinert D, Micari A, Cohen DJ, Wang H, Hasenbank MS, Jaff MR; IN.PACT SFA Trial Investigators. Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Le — View Citation

McKinsey JF, Zeller T, Rocha-Singh KJ, Jaff MR, Garcia LA; DEFINITIVE LE Investigators. Lower extremity revascularization using directional atherectomy: 12-month prospective results of the DEFINITIVE LE study. JACC Cardiovasc Interv. 2014 Aug;7(8):923-33. — View Citation

Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, Rutherford RB; TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease. Int Angiol. 2007 Jun;26(2):81-157. Review. — View Citation

Roberts D, Niazi K, Miller W, Krishnan P, Gammon R, Schreiber T, Shammas NW, Clair D; DEFINITIVE Ca?? Investigators. Effective endovascular treatment of calcified femoropopliteal disease with directional atherectomy and distal embolic protection: final re — View Citation

Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc Interv. 2014 May 1;83(6):E212-20. doi: 10.1002/ccd.25387. Epub 2014 Feb 10. Review. — View Citation

Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, Brodmann M, Pilger E, Zeller T, Krishnan P, Gammon R, Müller-Hülsbeck S, Nehler MR, Benenati JF, Scheinert D; LEVANT 2 Investigators. Trial of a Paclitaxel-Coated Balloon for Femo — View Citation

Scheinert D, Duda S, Zeller T, Krankenberg H, Ricke J, Bosiers M, Tepe G, Naisbitt S, Rosenfield K. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-hum — View Citation

Tepe G, Beschorner U, Ruether C, Fischer I, Pfaffinger P, Noory E, Zeller T. Drug-Eluting Balloon Therapy for Femoropopliteal Occlusive Disease: Predictors of Outcome With a Special Emphasis on Calcium. J Endovasc Ther. 2015 Oct;22(5):727-33. doi: 10.1177 — View Citation

Tepe G, Laird J, Schneider P, Brodmann M, Krishnan P, Micari A, Metzger C, Scheinert D, Zeller T, Cohen DJ, Snead DB, Alexander B, Landini M, Jaff MR; IN.PACT SFA Trial Investigators. Drug-coated balloon versus standard percutaneous transluminal angioplas — View Citation

Tepe G, Zeller T, Albrecht T, Heller S, Schwarzwälder U, Beregi JP, Claussen CD, Oldenburg A, Scheller B, Speck U. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008 Feb 14;358(7):689-99. doi: 10.1056/NEJM — View Citation

Werk M, Albrecht T, Meyer DR, Ahmed MN, Behne A, Dietz U, Eschenbach G, Hartmann H, Lange C, Schnorr B, Stiepani H, Zoccai GB, Hänninen EL. Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIF — View Citation

Werk M, Langner S, Reinkensmeier B, Boettcher HF, Tepe G, Dietz U, Hosten N, Hamm B, Speck U, Ricke J. Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Circulation. — View Citation

Yazdani SK, Pacheco E, Nakano M, Otsuka F, Naisbitt S, Kolodgie FD, Ladich E, Rousselle S, Virmani R. Vascular, downstream, and pharmacokinetic responses to treatment with a low dose drug-coated balloon in a swine femoral artery model. Catheter Cardiovasc — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Post procedure TVR	TVR within 6, 12, 24 months post index procedure	6, 12, 24 months
Secondary	CD-TLR post procedure	TLR within 6, 12, 24 months post index procedure	6, 12, 24 months
Secondary	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
Secondary	Major target limb amputation post procedure	Major target limb amputation within 6, 12, 24 months post index procedure	6, 12, 24 months
Secondary	Thrombosis- target lesion post procedure	Thrombosis at the target lesion site within 6, 12, 24 months post index procedure	6, 12, 24 months
Secondary	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	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

External Links

•   HawkOne 510(k) clearance.
•   Turbo Hawk 3 510(k) clearances.