Update on the OPTIMIZE BTK Trial. Marianne Brodmann, MD Division of Angiology Medical University Graz, Austria

Transcription

1 Update on the OPTIMIZE BTK Trial Marianne Brodmann, MD Division of Angiology Medical University Graz, Austria

2 Disclosure Speaker name: Marianne Brodmann, MD... I have the following potential conflicts of interest to report: x Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest

3 mm Limitation of Drug Coated Balloons in Calcified Lesions As circumferential calcium increases, the effectiveness of DCBs decreases Late lumen loss increased & primary patency decreased with calcium severity As calcium severity increases, late lumen loss at 6 months increases Severity of lesion calcification was a single independent predictor of late lumen loss outcome after DCB treatment 6-Month Mean Late Lumen Loss 0,8 0,6 0,4 0,2 0 0,07 None (N=30) P= ,24 0,74 Mild + Moderate Moderate severe (N=23) + severe (N=36) Calcification Dr. Fanelli s Calcium Impact on DCB Study (Prospective, 60 patients, SFA lesions treated with DCBs, 12 month follow-up) Dr. Tepe s Peripheral DCB Study (Retrospective, 91 patients, Fempop lesions treated with DCBs, 6 month follow-up) Fanelli F, et al. Cardiovasc Intervent Radiol. 2014; 37: Tepe G. et al. J Endovasc Ther. 2015;22:

4 Below the Knee DCB Studies Single center studies suggest DCBs may lower reintervention rates; however, RCTs have failed to show superiority of DCBs for BTK treatment Single-center studies 1-year results LEIPZIG No statistical differences RCTs 1-year results IN-PACT DEEP Not reported Not reported R E S T E N O S I S O C C L U S I O N T L R DEBATE-BTK p<0.001 p<0.001 p=0.002 CD- T L R M AJ O R AM P D E AT H M AE R E S T E N O S I S O C C L U S I O N T L R No statistical differences BIOLUX-II p<0.05 DEBELLUM p<0.05 Not reported R E S T E N O S I S O C C L U S I O N T L R CD- T L R M AJ O R AM P D E AT H M AE LEIPZIG: Schmidt A, et al. Catheter Cardiovasc Interv. 2010;76: ; Schmidt A, et al. J Am Coll Cardiol. 2011;58: DEBATE-BTK: Liistro F, et al. Circulation. 2013;128: DEBELLUM: Fanelli F, et al. J Cardiovasc Surg. 2014;55: IN.PACT-DEEP: Zeller T, et al. J Am Coll Cardiol. 2014;64: BIOLUX II: Zeller T, et al. J Am Coll Cardiol Intv. 2015;8:

5 STEALTH 360 Peripheral Orbital Atherectomy System Streamlined Setup and Treatment Sleek Electric-Powered Handle Simple device set-up Optimum torque transfer to the shaft and crown Short overall treatment times Crowns Micro Crown Classic Crown Solid Crown Instant Response On/Off Switch Simple Speed Settings Prime Control Flush saline device Brake OAS Pump Mounts directly to an I.V. pole Bathes shaft and crown with ViperSlide Lubricant to facilitate smooth device operation Crowns shown are the 1.25 mm Micro Crown, 1.50 mm Classic Crown, and 2.00 mm Solid Crown. Photographs are not to scale and for illustrative purposes only.

6 CSI s Unique MOA: Changing Compliance using Centrifugal Force 360 crown contact designed to create a smooth, concentric lumen Allows constant blood flow and particulate flushing during orbit 30 µm diamond coating eccentric-mounted mass Differential Sanding Pulsatile Forces 2 Before OAS After OAS Micro-particulate Average particulate size 1 = 2 µm Bi-directional sanding of superficial calcium Healthy elastic tissue flexes away from the crown, minimizing damage to the vessel Low frequency (18-40 Hz) represents crown orbit inside vessel* High frequency ( Hz) represents rotation of eccentric crown over the wire, producing pulsatile mechanical forces* These pulsatile forces may affect deeper plaque and contribute to compliance change** * In a phantom non-diseased popliteal artery ** Results vary based upon plaque morphology, calcification, and anatomy 1. Based on cadaver atherosclerotic lesions, porcine coronary lesions, and graphite blocks 2. Test models: Zheng Y, et al. Med Eng Phys. 2016;38(7):

7 Calcified Plaque Modification Alters Local Drug Delivery in the Treatment of Peripheral Atherosclerosis Untreated OAS Treated These data illustrate that calcified plaque limited intravascular drug delivery, and controlled OAS treatment of calcific plaques trended in greater drug permeability and improved adjunct drug delivery to diseased arteries. Study performed in 5 cadaveric lower limbs with calcified arteries. Freshly excised arterial segments were lumenally infused with a buffered solution (PBS/4% BSA) of radiolabeled (14C, 10 μm) or fluorescent (Oregon Green 488, 10 μm) paclitaxel. Tzafriri AR, et al. J Control Release. 2017;264:

8 OPTIMIZE-BTK OAS+DCB vs. DCB Alone in BTK Lesions Study Details: Pilot study Prospective, 1:1 Randomization Calcified below the knee lesions Study devices: Peripheral Orbital Atherectomy System (Cardiovascular Systems, Inc.) Lutonix 014 Drug Coated Balloon (C.R. Bard, Inc.) Evaluable subject: subject who met all of the inclusion and none of the exclusion criteria (angiographic criteria confirmed by the Core Lab) and alternative (non-study devices) or post-adjunctive treatment(s) were not required during the index procedure 2-year follow-up OAS + DCB N = Approx. 25 N = Approx. 65 N = 50 Evaluable Subjects DCB N = Approx. 25 Purpose: Demonstrate the ability of the OAS to prepare calcified, BTK lesions for optimal DCB deployment OPTIMIZE-BTK is sponsored by Cardiovascular Systems, Inc. (ClinicalTrials.gov NCT )

9 OPTIMIZE-BTK: Inclusion/Exclusion Criteria Notable Inclusion Criteria: Rutherford Clinical Category 3 5 Lesions [except in-stent restenosis (ISR)] of the distal POP (POP segment below the anatomical knee joint), AT, PT, TPT, and PR arteries with 70 % DS by angiography Presence of clearly visible calcification in two views (both sides of vessel at the same location) evaluated angiographically CT angio images may substitute to confirm distribution of calcium Length of calcium 25 % of total lesion length or 2 cm total length Target lesion length up to 20 cm Notable Exclusion Criteria: Presence of inflow lesion ( 50 % DS) or inflow not successfully treated ( 50 % DS and/or unresolved significant angiographic complication) Compromised outflow distal to the target lesion ( 70 % DS) or presence of lesion(s) or occlusion(s) located from 5 cm above the ankle to below the ankle joint space Subject has more than 2 target vessels requiring treatment Presence of significant ( 70 % DS) lesion(s) or occlusion(s) not meeting the study criteria which were not successfully treated during the index procedure ( 50 % DS and/or significant angiographic complication) Subject has planned amputation (including minor) of the index limb or previous major amputation of the contralateral limb

10 OPTIMIZE-BTK: Primary Outcome Measures LLL of the target lesion by QVA at 6 months post-procedure or at the time of TLR Patency of the target lesion by DUS at 6 mo and 12 mo postprocedure Freedom from Major Adverse Events at 30 days, 3, 6,12, and 24 months post-procedure MAEs include: clinically-driven TLR; unplanned, unavoidable major amputation of the index limb; and death within 30 days of the index procedure Freedom from clinically driven TLR at follow up (core lab adjudicated) Freedom from unplanned, unavoidable major amputation of the index limb follow up

11 OPTIMIZE-BTK: Study Update 53 subjects enrolled as of 16Jan2018 Active Sites: Austria (Prof. Brodmann/Deutschmann & Dr. Werner) Germany (Prof. Zeller, Prof. Tepe, Prof. Andrassy, Prof. Blessing, Prof. Scheinert) Switzerland (Dr. Banyai)

12 Conclusions Calcified lesions may reduce the efficacy of DCBs by blocking uptake of drug into vessel wall Preclinical data suggest OAS treatment of calcific plaques trended in greater drug permeability and improved adjunct drug delivery to diseased arteries OPTIMIZE-BTK trial is designed to test the hypothesis that pretreatment with OAS for calcified BTK arteries followed with DCB will provide incremental benefits versus DCB angioplasty alone 53 subjects enrolled as of 16Jan2018