Update on BEST-CLI Trial

Transcription

1 Update on BEST-CLI Trial Alik Farber, M.D. Professor and Chief Division of Vascular and Endovascular Surgery Boston Medical Center Boston University School of Medicine

2 Disclosures Trial Co-Chair Supported by NHLBI: 1U01HL A1

3

4 A Growing Problem Obesity Metabolic Syndrome Elderly PAD/CLI Diabetes

5 An Expensive Problem Medicare expenditure on CLI > $4 billion (CHF = $3.9B, Cerebrovascular disease = $3.7B) 90% inpatient care $1,700 per patient (>2X avg beneficiary) 3% of total Medicare budget (THR = 0.9%, TKR 1.7%)

6 Natural History of Critical Limb Ischemia >1,500 patients in 13 studies at 1 year f/u --22% mortality --35% worsening tissue loss --22% major amputation rate

7 Goals Of Treatment Medical therapy to optimize cardiovascular risk Measures to improve limb perfusion (revascularization) Relieve pain Heal wounds Preserve a functional limb Maintain ambulatory status Hirsch AT et al. J Am Coll Cardiol 2006;47: Conte MS and Farber A. BJS 2015;102:

8 Current State of Affairs in CLI Most CLI is treated with infrainguinal revascularization Bypass Surgery Endovascular Therapy

9 Current State of Affairs in CLI Most CLI is treated with infrainguinal revascularization There is great variation in amputation and revascularization rates in patients with CLI (Dartmouth Atlas, 1998) Amputation rates among certain groups are rising (Humphries JVS 2016) There is variability in intensity of vascular care across regions of the United States (Goodney. Circulation CV 2012) There is great variability in how open surgery and endovascular therapy is utilized to treat CLI (Menard. JAHA 2016)

10 Critical Limb Ischemia: % Treated by Bypass (vs. PVI) 100% 100% Bypass 90% 80% 70% 60% Procedure Selection Variation 50% 40% 30% 20% 10% 0% 0% Bypass VQI Centers

11 There is paucity of highquality data available to guide clinical decision making.

12 What about just trying endovascular therapy-first on every patient with CLI?

13 J Cardiovasc Surg (Torino) Dec;54(6): 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.

14 Bypass after endofailure is significantly less successful than primary bypass Amputation Free Survival Bypass first Bypass first Bypass after angioplast y Endovascular-first approach in all patients with CLI is a strategy that is not supported by good science... Bradbury A. J Vasc Surg 2010; 51(5 Suppl)5S-17S Nolan BW. J Vasc Surg 2011; 54:730-6

15

16 BEST-CLI Trial: Overview NIH-funded, prospective, randomized, multicenter, multispecialty, pragmatic, open-label superiority trial 2100 patients at 160 clinical sites Goal: to assess clinical outcomes, quality of life, cost and value in patients who are candidates for both vascular surgery and endovascular therapy

17 BEST-CLI is unique Well powered and designed Real world pragmatic trial Two cohort design SSGSV (optimal conduit) 1620 patients All conduits are allowed 480 patients Stratification by clinical presentation and anatomy Novel endpoints MALE-free Survival is optimal endpoint Death, amputations AND major re-interventions Hemodynamic success, clinical success Comprehensive quality & economic analysis planned All specialties involved Planned by a multidisciplinary group of CLI experts

18 BEST-CLI is positioned Provide a treasure trove of relevant data about CLI and its management

19 BEST-CLI is positioned Define an evidence-based standard of care Inform next set of scientific, clinically relevant questions

20 Current Status 20

21 Status of Sites and Investigators 162 Sites Activated 131 Sites Open for enrollment 23 Sites Closed 5 Sites Non-enrollment status 13 Sites in Start-up 928 Investigators 143 Cardiologists 129 Radiologists 7 Vascular Medicine Specialists 635 Vascular Surgeons 14 Other 2/3 of Sites are Multidisciplinary 21

22 Enrollment Update As of 2/15/2018 1,205 subjects randomized 895 to go!

23 What have we learned so far Patient Characteristics and Trial Compliance 23

24 Patient Characteristics (as of 11/5/2017 data freeze) 1,108 patients Cohort 1: 876 (79%) 77% predicted Cohort 2: 232 Cohort 1 Strata Rest pain, no tibial dz 8% Rest pain and tibial dz 12% Tissue loss, no tibial dz 23% Tissue loss and tibial dz 57%

25 Patient Characteristics (as of 11/5/2017 data freeze) Cohort 1 29% female 36% predicted 30% non-white race 27% predicted 16% Hispanic 13% predicted Median age: 67 years Bilateral CLI: 16%

26 Patient Characteristics (as of 11/5/2017 data freeze) Cohort 1 HTN: 87% DM: 72% CAD: 42% COPD: 13% CVA: 14% ESRD: 12% Smoking Hx: 75% Current smoking: 34% Any previous vascular intervention: 12% Any previous inflow reconstruction: 7%

27 Trial Compliance (as of 11/5/2017 data freeze) Trial compliance is excellent Withdrawal/Loss to follow-up rate: 4% Randomized procedure initiated first: 97%

28 What have we learned so far Specialty Participation and Comparison to Real World 28

29 Investigator Specialty in BEST-CLI as of 9/13/ physicians credentialed at 136 centers IR 14% IC 15% VS 69% VS IC IR VM other

30 Vascular Surgeons in BEST-CLI 596 physicians credentialed ENDO 1% OPEN 19% BOTH 69% Both Open Endo only Conditional both Conditional open

31 Comparison of Endovascular Investigator Specialty Percent 60 BEST-CLI vs National Medicare Claims BEST-CLI Medicare Claims VS IC IR other

32 Obstacles to Enrollment

33 Methods Designed a 12 item, multiple-choice, rating-scale survey to assess role of various barriers to enrollment Administered survey to investigators and coordinators at 30 high performing and 30 low performing sites High-performing sites (HPS) defined as: Enrollment frequency > 0.5 subjects/month > 8 total subjects enrolled Low-performing sites (LPS) defined as: Enrollment of at least 1 but less than 2 subjects

34 Findings Most common obstacles to enrollment: Difficulty with motivating patients and investigators to participate

35 Treatment Bias Tough Nut to Crack

36 BEST BUZZ BEST is going global University of Helsinki activated last week Sites in New Zealand, France, Italy, Germany are being onboarded Efforts on the way to obtain funding for a companion CLI registry that will include patients not eligible for the RCT New protocol amendment will reduce site burden Eliminate need for diagnostic angiogram Increase payment to subjects Allow for centralized follow-up Investigators Meeting, Washington, D.C., April 13 th

37 37

38 38