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Circulatory System Devices Advisory Panel

Circulatory System Devices Advisory Panel. LACI Review Introductions Outline of presentations Presentations. Introductions & History. Introductions. Chris Reiser PhD VP Technology & Clinical Research, Spectranetics John Laird MD , Washington Hospital Center LACI Principal Investigator

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Circulatory System Devices Advisory Panel

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  1. Circulatory System Devices Advisory Panel LACI Review • Introductions • Outline of presentations • Presentations Introductions & History

  2. Introductions • Chris Reiser PhD • VP Technology & Clinical Research, Spectranetics • John Laird MD, Washington Hospital Center • LACI Principal Investigator • Bruce Gray DO, Greenville Memorial Hosp, SC • LACI Steering Committee, Investigator • Venkatesh Ramaiah MD FACS, Arizona Heart • staff surgeon and LACI PI Introductions & History

  3. Outline of Presentations • Background and history • LACI Phase 2 results • Benefits of LACI • Why limb salvage is better than limb loss • Alternative treatment strategies 1 : medication 2 : primary amputation 3 : PTA 4 : bypass surgery • Summary of alternatives Introductions & History

  4. Basic Technology • Excimer laser atherectomy (ELA): • XeCl excimer laser, 308 nm, pulsed at 40 pulses/second maximum • Delivered via a fiberoptic catheter • First approved by FDA in 1993 for use in coronary arteries • Similar but slightly different than LASIK Introductions & History

  5. ELA 308 nm fiber delivery catheters arteries & veins “cool” UV ablation LASIK 193 nm free-air propagation work station corneas “cool” UV ablation Quick Comparison Introductions & History

  6. CVX-300 Laser System • Gen 4 approved 1994? • Same system used for all our applications: • coronary atherectomy • pacing lead removal • peripheral atherectomy (EU only) • A few facts... Introductions & History

  7. Excimer Laser Catheters • 4th generation since first FDA approval • Latest models are “legs-only” devices • All have same basic features and work the same way Introductions & History

  8. How ELA Works... Introductions & History

  9. How ELA Works... Introductions & History

  10. How ELA Works... Introductions & History

  11. Coronary Indications • Long, diffuse lesions • Total occlusions crossable with a wire • Moderately calcified lesions • Ostial lesions • Balloon angioplasty failures • Vein grafts • In-stent restenosis prior to brachytherapy Introductions & History

  12. ELA Experience in the Legs • Initial IDE work in the USA - early ‘90s • Commercial experience in EU since ‘95? • Anecdotal single-site experiences • LACI Phase 1 • LACI Phase 2 Introductions & History

  13. Laser Angioplasty for Critical Limb Ischemia Results of the LACI Phase 2 Registry LACI 2 Results

  14. Study Design • Prospective, multi-center study • Patients with CLI • Rutherford Category 4-6 • poor surgical candidates • Treatment: ELA of SFA, popliteal and/or infrapopliteal arteries, with adjunctive PTA and optional stenting • Primary Efficacy Endpoint: limb salvage at 6 mo. • freedom from amputation at or above the ankle • Primary Safety Endpoint: death at 6 mo. LACI 2 Results

  15. Study Design • Included catheters: • 2.2 - 2.5mm Spectranetics peripheral laser catheters • any Spectranetics coronary laser catheter • Poor surgical candidates because: • poor or absent vessel for outflow anastamosis, or • absence of venous conduit, or • significant co-morbidity • Enrollment period: April ‘01 - April ’02 • Enrollment: 145 patients, 155 limbs LACI 2 Results

  16. Historical Control Group • Italian multicenter randomized study of Prostaglandin E1 in CLI patients • 771 in alprostadil group • 789 in control group • Control group received variety of therapies (bypass, endarterectomy, medication, and a few PTAs) • “the best you can do” for these patients • Ann Intern Med 1999; 130:412-421 • Conforms to TASC definitions and GCP

  17. Enrollment by Site • 145 patients at 14 sites Arizona Heart 23 Hertzentrum Leipzig 24 Hertzentrum Bad Kroz. 22 Greenville Memorial 19 Manatee Hospital 10 Lankanau Memorial 8 Riverside Methodist 7 Glendale Memorial 7 St. Joseph’s Paterson 7 Univ. Frankfurt 6 Springhill Memorial 5 Washington HC 5 Ochsner Clinic 1 St. Luke’s Milwaukee 1 total patients 145 total legs 155 • 36% of sites enrolled 68% of patients LACI 2 Results

  18. Patient Descriptors LACIControlp Mean age, years 72 ± 10 72 ± 10 ns Men 53% 72% * Risk factors Smoking current 14% 25% * Prior MI 23% 15% * Prior stroke 21% 12% * Diabetes mellitus 66% 39% * Hypertension 83% 49% * Dyslipidemia 56% 16% * Obesity 35% 7% * *significant LACI 2 Results

  19. Leg Descriptors LACIControlp Rutherford Category 4 27% 30% ns 5 or 6 72% 70% ns Reasons for poor surgical candidacy Absence of venous graft 32% Poor/no distal vessel 68% High surgical risk 46% 11% * Only one reason 61% Any two reasons 33% All three reasons 6% LACI 2 Results

  20. Case Profile • 61 year old Hispanic woman • Diabetic for > 20 years • ESRD; hemodialysis for 1 year • Non-smoker • Multiple ischemic ulcers on both feet • Bilateral ELA on 14 Aug 01 • Skin grafts during follow-up period • Investigator: Dr. Mitar Vranic at Arizona Heart LACI 2 Results

  21. Case Profile : Right Foot 1/4 Prior to treatment LACI 2 Results

  22. Case Profile : Right Foot 2/4 • 2.2 mm laser • 3.0 mm balloon • no stent • popliteal also treated LACI 2 Results

  23. Case Profile : Right Foot 3/4 3 months post treatment LACI 2 Results

  24. Case Profile : Right Foot 4/4 6 months post treatment LACI 2 Results

  25. Case Profile : Left Foot 3 months baseline laser balloon no stent 6 months LACI 2 Results

  26. LACI 2 Results

  27. LACI 2 Results

  28. Case Profile • 45 year old female • Diabetes mellitus, morbid obesity • Distal popliteal occlusion, tibial disease • Painful, ischemic 2nd toe LACI 2 Results

  29. SITE 009-WHC PAT 005 6 MOS LACI 2 Results

  30. Vascular Lesion Locations 45% 40% 35% 30% 25% % of Identified Lesions 20% 15% 10% 5% 0% SFA popliteal infrapopliteal other LACI 2 Results

  31. Lesion Types Mean # of treated lesions/pt: 2.7  1.4 (1-7) 80% 70% 60% 50% % of Limbs 40% 30% 20% 10% 0% stenoses occlusions stenoses and occlusions LACI 2 Results

  32. TASC Types LACI 2 Results

  33. LACI Procedure Results Guidewire crossing success 92% Laser treatment delivered 99% Adjunctive balloon 96% Stent Placement 45% Procedure Success 85% <50% residual stenosis at final Straight line flow to foot established 89% Hospital stay (days): mean 3.0 median 1.0 LACI 2 Results

  34. Angiographic ResultsVisual assessment • %DS • LocationBaselinePost-laserFinal • SFA 91% 56% 16% • Popliteal 94% 53% 14% • Infrapopliteal 92% 53% 24% • Laser provided about half of the net luminal gain • Stenting was performed preferentially in larger vessels • Below the knee, final %DS was slightly higher LACI 2 Results

  35. Control Treatments Bypass or endarterectomy 35% Angioplasty 5% Thrombectomy 3% Conservative therapies 57% • analgesics, vasoactive, antithrombotic, oxygen therapy, etc. LACI 2 Results

  36. Adjudicated SAEs LACI Control p Death 10% 14% ns Major amputation 6% 10% ns Nonfatal MI or Stroke .7% 1.1% ns Reintervention 17% 4% * Hematoma w/ surgery .7% .8% ns Acute limb ischemia .7% n/a Perforation w/ surgery 0 n/a Bypass 2.1% n/a Endarterectomy .7% n/a Total SAEs 38% 30% ns LACI 2 Results

  37. 6-Month Results: Patients Total enrollment 145 patients death 15 lost to follow-up 11 Reached 6-month follow-up 119 Major amputation in survivors 9 Patients with limb salvage 110 Intent-to-treat analysis 110/145 = 76% Survival analysis 110/119 = 92% LACI 2 Results

  38. 6-Month Results: Limbs Total enrollment 155 limbs death 17 lost to follow-up 11 Reached 6-month follow-up 127 Major amputation in survivors 9 Limbs salvaged 118 Intent-to-treat analysis 118/155 = 76% Survival analysis 118/118 = 93% LACI 2 Results

  39. Main Endpoints at 6 Months LACIControlp n 145 673 Died 10% 14% ns Survived with: Limb salvage 76% 73% ns Persistent CLI 30% 31% ns Any SAE* 38% 30% ns * Including reinterventions not originally termed SAE’s under protocol LACI 2 Results

  40. Ulcer Sizes per-ulcer basis Most healing occurred in the first 3 months LACI 2 Results

  41. Functional Outcomes Of surviving legs: 69% Improved 27% Stable 4% Declined LACI 2 Results

  42. Predictors of Events • Major Amputationp • Category 6 .03 • Previous minor amputation .05 • Death • Age .03 • by Cox proportional hazards modeling LACI 2 Results

  43. Stenting Stented Not Stented n=70n=85 p Procedure Success 93% 79% .01 Straight-line flow 96% 84% .02 Limb Salvage 83% 71% .09 p-values by Fisher’s Exact • Stents improved acute results • Stents did not significantly affect limb salvage • Sample size is small (low statistical power) LACI 2 Results

  44. LACI Phase 2 Summary • Treatment of complex disease – multiple stenoses and occlusions • High risk patient population – poor candidates for surgical revascularization • High procedural success with few in-hospital SAE’s and short hospital stay • Excellent limb salvage rate despite this high-risk patient cohort LACI 2 Results

  45. LACI Phase 2 Summary • Outcomes met all hypotheses in the protocol • Statistics meet the benchmarks of safety and effectiveness LACI 2 Results

  46. Clinical Benefit of LACI • The LACI treatment strategy salvaged limbs... • Efficacy endpoint equaled “the best” benchmarks in the literature • …without affecting patient’s chances of survival... • Safety endpoint equaled “the best” • …or significantly increasing patients’ risk of serious adverse events. Benefits

  47. Clinical Benefit of LACI • LACI is an intravascular intervention • avoids perioperative risks of surgery • shortens initial hospital stay • does not jeopardize future surgical options and may create new surgical options • LACI Phase 2 results were achieved with virtually no surgery Benefits

  48. Clinical Benefit of LACI • The LACI strategy is applicable to a wide range of vascular disease states • not limited to lesions amenable to PTA • LACI Phase 2 enrolled essentially “all comers” • useful in patients with no other options for limb salvage • LACI results are predictable • high rate of procedure success Benefits

  49. Technical Benefit • ELA reduces a complex lesion pattern into something that balloons and (optional) stents can handle... Benefits

  50. Normal Post Laser 3mm Balloon Final Baseline Progressive Simplification Benefits

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