BEST-CLI: What Will This Trial Do For You? BEST-CLI Trial Co-Chair - - PowerPoint PPT Presentation

4/16/2016 1

BEST-CLI:

What Will This Trial Do For You?

Matthew T. Menard, M.D Brigham & Women’s Hospital

Disclosures

BEST-CLI Trial Co-Chair

Supported by NHLBI: 1U01HL107407-01A1 Alive with 2 Limbs 45%

Natural History of CLI

Critical Limb Ischemia

(Rest Pain, Ulceration or Gangrene)

1-Year Outcomes

Mortality 25% Amputation 30%

Hirsh et al. JACC. 2006;47:1239-1312.

Continued CLI 20% CLI Resolved 25%

Goodney et al. J Vasc Surg 2009;50:54-60

Trends in PAD Therapy

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J Cardiovasc Surg (Torino). 2013 Dec;54(6):679-84. Endovascular first as "preliminary approach" for critical limb ischemia and diabetic foot. Setacci C1, Sirignano P, Galzerano G, Mazzitelli G, Sauro L, de Donato G, Benevento D, Cappelli A, Setacci F.

Mahoney E M et al. Circ Cardiovasc Qual Outcomes 2010;3:642-651

“ One-year and cumulative 2-year costs ($) associated with hospitalizations for vascular reasons, per patient, by baseline PAD class:

Reach Registry Revascularization Options in CLI

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Which is best?

What is current state

• f evidence

Tunis et al.

11

Limitations of Current Data

• Retrospective
• Poorly controlled
• Suboptimal endpoints
• Amputation free survival
• Target lesion revascularization
• Target vessel revascularization
• Patency
• Sponsor bias
• Operator bias
• Inclusion of claudicants
• Short or incomplete follow up

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Publications reporting 1-yr patency following SFA stenting or stent-grafting from 2000-2009

1-yr Patency after Endovascular Intervention in the SFA

Drug – elution ?

SFA-Popliteal DCB Trials

6-month Late Lumen Loss in SFA-Popliteal DEB Trials

J Lammer LINC 2014

“Endo Technological Breakthroughs”

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Large RCT’s for Vascular Disease

• Carotid Endarterectomy
• NASCET, ACAS, ACST, VA

Trial, ECST,GALA

• CEA vs Carotid Stent
• ACT I, CREST,

CASANOVA,EVA 3s, ICSS, SAPPHIRE, SPACE, CAVATAS

• AAA
• ADAM, UK Small AAA
• AAA vs EVAR
• DREAM I and II, EVAR

I and II, OVER , ACE, Numerous IDE studies.

• CLI: Bypass vs Endo
• BASIL

BASIL Trial

• Aim: To compare outcomes of surgery-first strategy with

angioplasty first strategy in patients with CLI

• Results:
• No significant difference in amputation-free survival at >5

year follow-up

• Trend toward benefit for surgery noted in those patents

who survived more than 2 years

• Limitations:
• Underpowered
• Endovascular therapy limited to angioplasty
• Lack of lesion standardization
• 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….

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Variation in Amputation Rates Among Patients with CLI

Dartmouth Atlas of Cardiovascular and Thoracic Healthcare Care. Manning Selvage & Lee; 1998

Variation in LE Revascularization

Goodney P et al. Circ Cardiovasc Qual Outcomes. 2012;5:94-102 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

All VQI Centers Mean = 31%

Critical Limb Ischemia: % Treated by Bypass (vs. PVI)

0% Bypass 100% Bypass

Procedure Selection Variation

VQI Centers

Equipoise The current state of CLI treatment The current state of CLI treatment

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BEST-CLI Trial: Overview

• Prospective, randomized, multicenter, open-label

superiority trial

• 2100 patients at 140 clinical sites in United States and

Canada

• Funded by National Heart Lung and Blood Institute

Goal: to assess outcomes, quality of life and cost in

patients who are candidates for both open and endovascular therapy

Two Cohort Design

• Cohort #1 Patients with single segment great

saphenous vein (SSGSV) N=1620

Open surgery vs. Endovascular treatment

• Cohort #2 Patients without SSGSV N=480

(arm vein, short saphenous vein, composite vein, cryopreserved vein, and prosthetic conduit)

Open surgery vs. Endovascular treatment

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Matthew Menard, MD

Why is BEST-CLI Important?

Positioned to answer questions BASIL, registries and non-RCT data-sets cannot

Real world pragmatic trial Multi-disciplinary – everyone involved Two cohort design – all conduits allowed Novel primary and secondary endpoints

• Major Adverse Limb Event (MALE) - free survival

Additional Secondary Endpoints

• Freedom from hemodynamic failure
• Freedom from clinical failure
• Freedom from critical limb ischemia
• Number of re-interventions per limb salvaged
• Freedom from re-interventions (major and minor) in index limb

Key Secondary Endpoints

• Re-intervention and Amputation-free Survival (RAS)
• Amputation-free Survival
• MALE-POD

Clinical outcomes

A typical trial

CEA alongside a prospective study

$$ $ $$$ $$ $ $ $ $ $ $ $

4/16/2016 9 The approach we’re taking in BEST

$$ $ $$$ $$ $ $ $ $ $ $ $ $$ $ $$$ $$ $ $ $ $ $ $ $ MEASUREMENT MODELING

Quality Adjusted Life Years (QALYs)

• 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

• utcomes.

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1 3 12 24 36 48 Quality of Life (e.g.EQ-5D) Follow-up month

Quality of Life

Open Endo 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1 3 12 24 36 48 EQ-5D Follow-up month

Quality Adjusted Life Years

Open Endo

34

Map of BEST-CLI Sites

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BEST-CLI Investigators

• 138 Cardiologists
• 116 Radiologists
• 6 Vascular Medicine Specialists
• 526 Vascular Surgeons
• 2 Cardiothoracic Surgeons

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Current status

• 1st patient randomized August, 2014

121 Sites open for enrollment 538 Patients randomized

• 435 in Cohort #1
• 101 in Cohort #2

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Enrollment

38 Matthew Menard, MD

BEST-CLI Is Unique

• Positioned to

– Assess the role of endovascular and open surgery when optimal conduit 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

Define an evidence-based standard of care.