4/16/2016 Disclosures BEST-CLI: What Will This Trial Do For You? BEST-CLI Trial Co-Chair � Supported by NHLBI: 1U01HL107407-01A1 Matthew T. Menard, M.D Brigham & Women’s Hospital Trends in PAD Therapy Natural History of CLI Critical Limb Ischemia (Rest Pain, Ulceration or Gangrene) 1-Year Outcomes Mortality Amputation Alive with 2 Limbs 30% 25% 45% Continued CLI CLI Resolved 20% 25% Goodney et al. J Vasc Surg 2009;50:54-60 Hirsh et al. JACC . 2006;47:1239-1312. 1
4/16/2016 J Cardiovasc Surg (Torino). 2013 Dec;54(6):679-84. Endovascular first as "preliminary approach" for critical limb ischemia and diabetic foot. Setacci C 1 , Sirignano P, Galzerano G, Mazzitelli G, Sauro L, de Donato G, Benevento D, Cappelli A, Setacci F. Reach Registry Revascularization Options in CLI One-year and cumulative 2-year costs ($) associated with hospitalizations for vascular reasons, per patient, by baseline PAD class: “ Mahoney E M et al. Circ Cardiovasc Qual Outcomes 2010;3:642-651 2
4/16/2016 What is current state Which is best? of evidence Tunis et al. Limitations of Current Data � Retrospective � Poorly controlled � Suboptimal endpoints o Amputation free survival o Target lesion revascularization o Target vessel revascularization o Patency � Sponsor bias � Operator bias � Inclusion of claudicants � Short or incomplete follow up 11 3
4/16/2016 1-yr Patency after Endovascular Intervention in the SFA Drug – elution ? Publications reporting 1-yr patency following SFA stenting or stent-grafting from 2000-2009 “Endo Technological Breakthroughs” SFA-Popliteal DCB Trials 6-month Late Lumen Loss in SFA-Popliteal DEB Trials J Lammer LINC 2014 4
4/16/2016 Large RCT’s for Vascular Disease BASIL Trial � Aim : To compare outcomes of surgery-first strategy with angioplasty first strategy in patients with CLI � Carotid Endarterectomy � AAA vs EVAR � Results : • • NASCET, ACAS, ACST, VA DREAM I and II, EVAR o No significant difference in amputation-free survival at >5 Trial, ECST,GALA I and II, OVER , ACE, year follow-up Numerous IDE o Trend toward benefit for surgery noted in those patents studies. � CEA vs Carotid Stent who survived more than 2 years • ACT I, CREST, � Limitations: CASANOVA,EVA 3s, � CLI: Bypass vs Endo o ICSS, SAPPHIRE, SPACE, Underpowered CAVATAS • o BASIL Endovascular therapy limited to angioplasty � AAA o Lack of lesion standardization • o ADAM, UK Small AAA Suboptimal primary endpoint Adam DJ. Lancet. Dec 3 2005;366(9501):1925-1934 Bradbury A. J Vasc Surg 2010; 51(5 Suppl)5S-17S …There is paucity of high-quality data available to guide clinical decision making…. 5
4/16/2016 Variation in Amputation Rates Among Variation in LE Revascularization Patients with CLI Goodney P et al. Circ Cardiovasc Qual Outcomes. 2012;5:94-102 Dartmouth Atlas of Cardiovascular and Thoracic Healthcare Care. Manning Selvage & Lee; 1998 Equipoise The current state of CLI treatment The current state of CLI treatment Critical Limb Ischemia: % Treated by Bypass (vs. PVI) All VQI Centers Mean = 31% 100% Bypass 100% 90% 80% 70% Procedure Selection Variation 60% 50% 40% 30% 20% 10% 0% VQI Centers 0% Bypass 6
4/16/2016 BEST-CLI Trial: Overview Two Cohort Design � Prospective, randomized, multicenter, open-label Cohort #1 Patients with single segment great � superiority trial saphenous vein (SSGSV) N=1620 � 2100 patients at 140 clinical sites in United States and Open surgery vs. Endovascular treatment Canada Cohort #2 Patients without SSGSV N=480 � Funded by National Heart Lung and Blood Institute � (arm vein, short saphenous vein, composite vein, cryopreserved vein, and prosthetic conduit) Goal: to assess outcomes, quality of life and cost in Open surgery vs. Endovascular treatment patients who are candidates for both open and endovascular therapy 7
4/16/2016 Key Secondary Endpoints Why is BEST-CLI Important? • Re-intervention and Amputation-free Survival (RAS) Positioned to answer questions BASIL, registries • Amputation-free Survival and non-RCT data-sets cannot • MALE-POD � Real world pragmatic trial Additional Secondary Endpoints � Multi-disciplinary – everyone involved • Freedom from hemodynamic failure � Two cohort design – all conduits allowed • Freedom from clinical failure • Freedom from critical limb ischemia � Novel primary and secondary endpoints • Number of re-interventions per limb salvaged • Major Adverse Limb Event (MALE) - free survival • Freedom from re-interventions (major and minor) in index limb Matthew Menard, MD A typical trial CEA alongside a prospective study $$ $ $$$ $$ $ Clinical outcomes $ $ $ $ $ $ 8
4/16/2016 Quality Adjusted Life Years (QALYs) The approach we’re taking in BEST Quality Adjusted Life Years (QALYs) will be calculated based on � area under the curve of quality of life for each patient. The average QALYs in two intervention arms then will be compared as outcomes. $$ $ $$$ $$ $ $$ $ $$$ $$ $ Quality of Life Quality Adjusted Life Years 1 1 0.9 0.9 0.8 0.8 Quality of Life (e.g.EQ-5D) 0.7 0.7 $ $ $ $ $ $ $ $ $ $ $ $ 0.6 0.6 EQ-5D 0.5 0.5 Open Open 0.4 0.4 Endo Endo MEASUREMENT MODELING 0.3 0.3 0.2 0.2 0.1 0.1 0 0 0 1 3 12 24 36 48 0 1 3 12 24 36 48 Follow-up month Follow-up month 34 Map of BEST-CLI Sites BEST-CLI Investigators 138 Cardiologists � 116 Radiologists � 6 Vascular Medicine Specialists � 526 Vascular Surgeons � 2 Cardiothoracic Surgeons � 35 9
4/16/2016 Current status Enrollment 1 st patient randomized August, 2014 � � 121 Sites open for enrollment � 538 Patients randomized • 435 in Cohort #1 • 101 in Cohort #2 37 38 BEST-CLI Is Unique • Positioned to – Assess the role of endovascular and open surgery when optimal conduit Define an evidence-based standard of care. is present – Assess the role of endovascular and open surgery when optimal conduit is not present – Assess outcomes as they relate to: • tibial disease, clinical presentation, gender, race, age, diabetes, heel ulcer, renal dysfunction – Prospectively validate the SVS WIFI classification and OPG endpoints Matthew Menard, MD 10
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