Best Endovascular vs. Best Surgical Therapy in Patients With Critical Limb Ischemia (BEST-CLI)

Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia

This study will compare the effectiveness of best available surgical treatment with best available endovascular treatment in adults with critical limb ischemia (CLI) who are eligible for both treatment options.

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Procedure: Open surgical revascularization; Device: Endovascular revascularization

Detailed Description

Male and female subjects aged 18 years or older will be randomized to receive either open surgical treatment or endovascular treatment. They will be followed for at least 2 years and up to 4 years and 2 months after treatment to primarily assess survival and major adverse limb events in the index or treated limb, and secondarily, to determine clinical and cost effectiveness outcomes after treatment. These outcomes (survival-free of major limb events and clinical, functional and cost effectiveness) will be compared within two cohorts of subjects: those with an available single-segment great saphenous vein, and those with an alternative conduit. The null hypotheses for both cohorts is that there will be no difference in MALE-free survival between best endovascular therapy and best surgical therapy.

• Study Type: Interventional
• Enrollment (Actual): 1843
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H3A7
      • Queen Elizabeth II Health Science Center
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • University of Western Ontario
    • Ottawa, Ontario, Canada, K1Y4E9
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A1A1
      • McGill
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hostpital
    • Quebec City, Quebec, Canada, G1L 3L5
      • CHU de Québec
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • Regina Qu'Appelle
    • Saskatoon, Saskatchewan, Canada, S7M0Z9
      • St. Paul's Hospital
• Finland
  • Helsinki, Finland, F100029
    • Helsinki University Hospital
• Italy
  • Florence, Italy, 50124
    • San Giovanni di Dio Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Auckland City Hospital
  • Waikato
    • Hamilton, Waikato, New Zealand, 3240
      • Waikato Hospital
  • Wellington
    • Newtown, Wellington, New Zealand, 6021
      • Wellington Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Heart Hospital
    • Tucson, Arizona, United States, 85719
      • University of Arizona - Banner University Medical Center
    • Tucson, Arizona, United States, 85745
      • Carondelet Heart & Vascular Institute
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas For Medical Services
  • California
    • Irvine, California, United States, 92697
      • University of California - Irvine
    • La Jolla, California, United States, 92037
      • UC San Diego Sulpizio Cardiovascular Center
    • La Jolla, California, United States, 92037
      • San Diego VAMC
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Loma Linda, California, United States, 92357
      • Loma Linda VA Medical Center
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles
    • Los Angeles, California, United States, 90089
      • Keck Medical Center of USC
    • Los Angeles, California, United States, 90095
      • UCLA-Gonda Vascular Surgery
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • Sacramento, California, United States, 95655
      • Sacramento VA Medical Center
    • San Diego, California, United States, 92123
      • Kaiser Permanente (San Diego)
    • San Francisco, California, United States, 94121
      • San Francisco Veterans Affairs Medical Center
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Northern California
    • San Francisco, California, United States, 94143
      • University of California-San Francisco Medical Center
    • Stanford, California, United States, 94305
      • Stanford hospital
    • Torrance, California, United States, 90509
      • Harbor - UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Denver, Colorado, United States, 80024
      • Denver Health
    • Denver, Colorado, United States, 80218
      • Vascular Institute of the Rockies
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Regional VA
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • St. Francis Hospital and Medical Center
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital
    • West Haven, Connecticut, United States, 06516
      • West Haven VAMC
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20037
      • GW Medical Faculty Associates, Inc.
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida (Gainesville)
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami
    • Miami Springs, Florida, United States, 33140
      • Mount Sinai Miami
    • Ocala, Florida, United States, 34471
      • Florida Hospital Ocala
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Tampa, Florida, United States, 33612
      • Tampa VAMC
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Foundation Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
    • Chicago, Illinois, United States, 60190
      • Central DuPage Hospital (Cadence)
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Winfield, Illinois, United States, 601611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical School
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Mercy Hospital Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
    • Shreveport, Louisiana, United States, 71130
      • University Health System: LSU Health Sciences
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Medstar Union Memorial Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical System
    • Baltimore, Maryland, United States, 21210
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21210
      • Loyola University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02132
      • VA Boston Healthcare System
    • Brighton, Massachusetts, United States, 02135
      • Steward St. Elizabeth's Medical Center
    • Weymouth, Massachusetts, United States, 02189
      • South Shore Hospital
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor Healthcare System
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Heart/St. Joseph Mercy Ann Arbor Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Flint, Michigan, United States, 48507
      • Michigan Vascular Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VAMC
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Hospital/Abbott Northwestern Hosp.
    • Rochester, Minnesota, United States, 55901
      • Mayo Clinic
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
    • Kansas City, Missouri, United States, 64116
      • Midwest Aortic Vascular Institute
    • Saint Louis, Missouri, United States, 63106
      • St. Louis VA Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Hanover, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart and Lung Center
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Heart Institute
    • Albuquerque, New Mexico, United States, 87108
      • New Mexico VA Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14215
      • VA Western NY Healthcare System
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Queensbury, New York, United States, 12804
      • Vascular Health Partners
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Stony Brook, New York, United States, 11794-8191
      • Stony Brook Medicine
    • Syracuse, New York, United States, 13215
      • SUNY Upstate Medical University
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
    • Durham, North Carolina, United States, 27705
      • Durham VAMC
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Heart and Vascular Research
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland/Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research Institute
    • Toledo, Ohio, United States, 43615
      • University of Toledo Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74135
      • University of Oklahoma College of Medicine at Tulsa
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97239
      • Portland VA Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Heart and Vascular Institute
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health System
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital/Brown Medical School
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health-Upstate (Formerly Greenville Memorial Hospital)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • North Central Heart Institute
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Medical Center
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Dallas VA Medical Center
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital TMC
    • Temple, Texas, United States, 76508
      • Scott and White - Temple
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • The University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialists
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute at Virginia Mason
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Clinical Trials Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health System
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin-Madison
    • Madison, Wisconsin, United States, 53713
      • Meriter Wisconsin Heart
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Milwaukee VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age 18 years or older.
2. Infrainguinal PAOD (occlusive disease of the arteries below the inguinal ligament).
3. CLI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain consistent with Rutherford categories 4-6.
4. Candidate for both endovascular and open infrainguinal revascularization as judged by the treating investigators
5. Adequate aortoiliac inflow.
6. Adequate popliteal, tibial or pedal revascularization target defined as an infrainguinal arterial segment distal to the area of stenosis/occlusion which can support a distal anastomosis of a surgical bypass.
7. Willingness to comply with protocol, attend follow-up appointments, complete all study assessments, and provide written informed consent.

Exclusion Criteria:

1. Presence of a popliteal aneurysm (>2 cm) in the index limb.
2. Life expectancy of less than 2 years due to reasons other than PAOD.
3. Excessive risk for surgical bypass (as determined by the operating surgeon and the CLI Team)
4. Planned above ankle amputation on ipsilateral limb within 4 weeks of index procedure.
5. Active vasculitis, Buerger's disease, or acute limb-threatening ischemia
6. Any prior index limb infrainguinal stenting or stent grafting associated with significant restenosis within 1 cm of stent or stent-graft, unless the occlusion/restenosis site is outside the intended treatment zone (i.e.,. a tibial vessel that is not currently intended to be revascularized as a part of the treatment for CLI).

7. Any of the following procedures performed on the index limb within 3 months prior to enrollment:

   1. Infrainguinal balloon angioplasty, atherectomy, stent, or stentgraft;
   2. Infrainguinal bypass with either venous or prosthetic conduit
8. Open surgical inflow procedure (aortofemoral, axillofemoral, iliofemoral, thoracofemoral or femorofemoral bypass) within 6 weeks prior to enrollment
9. Current chemotherapy or radiation therapy.
10. Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) which would preclude patient participation in angiographic procedures.
11. Pregnancy or lactation.
12. Administration of an investigational drug for PAD within 30 days of randomization.
13. Participation in a clinical trial (except observational studies) within the previous 30 days.
14. Prior enrollment or randomization into BEST-CLI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Available vein, open surg. revasc.; Subjects with an available SSGSV cohort randomized to open surgical revascularization	Procedure: Open surgical revascularization
Other: Available vein, endovasc. revasc.; Subjects with an available SSGSV cohort randomized to endovascular revascularization	Device: Endovascular revascularization; A variety of FDA approved devices will be used within this treatment arm. The trial will submit a proof-of-concept IDE application to the FDA to cover all devices.
Other: Alternative conduit, open surg. revasc.; Subjects with an alternative conduit cohort randomized to open surgical revascularization	Procedure: Open surgical revascularization
Other: Alternative conduit, endovasc. revasc.; Subjects with an alternative conduit cohort randomized to endovascular revascularization	Device: Endovascular revascularization; A variety of FDA approved devices will be used within this treatment arm. The trial will submit a proof-of-concept IDE application to the FDA to cover all devices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary efficacy endpoint: MALE (Major Adverse Limb Event)-free survival. MALE is defined as above ankle amputation of the index limb or major re-intervention (e.g. new bypass graft, jump/interposition graft revision, or thrombectomy/ thrombolysis)	Time to major adverse limb event or death, whichever occurs first in subjects with Single-Segment Great Saphenous Vein (SSGSV) available; Time to major adverse limb event or death, whichever occurs first in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical: Re-intervention and amputation-free survival (cohort 1)	Time to re-intervention of the index leg, above ankle amputation of the index leg, or death, whichever occurs first in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Re-intervention and amputation-free survival (cohort 2)	Time to re-intervention of the index leg, above ankle amputation of the index leg, or death, whichever occurs first in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from MALE-POD (POD, defined as death within 30 days of index procedure) (cohort 1)	Time to re-intervention of the index leg, amputation of the index leg, or death within 30 days of index procedure, whichever occurs first in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Clinical: Freedom from MALE-POD (POD, defined as death within 30 days of index procedure) (cohort 2)	Time to re-intervention of the index leg, amputation of the index leg, or death within 30 days of index procedure, whichever occurs first in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Amputation-free survival (cohort 1)	Time to amputation of the index leg, or death, whichever occurs first in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Amputation-free survival (cohort 2)	Time to amputation of the index leg, or death, whichever occurs first in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from POD (POD, defined as death within 30 days of index procedure) (cohort 1)	Time to death within 30 days of index procedure in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom POD (POD, defined as death within 30 days of index procedure) (cohort 2)	Time to death within 30 days of index procedure in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from Myocardial Infarction (cohort 1)	Time to myocardial infarction (MI) in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from Myocardial Infarction (cohort 2)	Time to myocardial infarction (MI) in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from Stroke (cohort 1)	Time to stroke in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from Stroke (cohort 2)	Time to stroke in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from re-intervention (major and minor) in index leg (cohort 1)	Time to re-intervention (major and minor) in index leg in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from re-intervention (major and minor) in index leg (cohort 2)	Time to re-intervention (major and minor) in index leg in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Number of re-interventions (major and minor) in per limb salvaged (cohort 1)	Number of re-interventions (major and minor) in per limb salvaged in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Number of re-interventions (major and minor) in per limb salvaged (cohort 2)	Number of re-interventions (major and minor) in per limb salvaged in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from hemodynamic failure (cohort 1)	Time to hemodynamic failure in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from hemodynamic failure (cohort 2)	Time to hemodynamic failure in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from clinical failure (cohort 1)	Time to above ankle amputation, major reintervention, MALE, degradation of WIfI stage or death, whichever occurs first in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from clinical failure (cohort 2)	Time to above ankle amputation, major reintervention, MALE, degradation of WIfI stage or death, whichever occurs first in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from Critical Limb Ischemia (CLI) (cohort 1)	Time to resolution of presenting CLI symptoms in the index limb in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from Critical Limb Ischemia (CLI) (cohort 2)	Time to resolution of presenting CLI symptoms in the index limb in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from all-cause mortality (cohort 1)	Time to all-cause mortality in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Clinical: Freedom from all-cause mortality (cohort 2)	Time to all-cause mortality in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Quality of Life assessment using VasuQoL (cohort 1)	VasuQOL measurements in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Quality of Life assessment using VasuQoL (cohort 2)	VasuQOL measurements in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Quality of Life assessment using EuroQoL (cohort 1)	EuroQOL measurements in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Quality of Life assessment using EuroQoL (cohort 2)	EuroQOL measurements in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Function assessment using SF-12, PCS (cohort 1)	Physical Component Summary (PCS) scores in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Function assessment using SF-12, PCS (cohort 2)	Physical Component Summary (PCS) scores in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Function assessment using SF-12, MCS (cohort 1)	Mental Component Summary (MCS) scores in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Function assessment using SF-12, MCS (cohort 2)	Mental Component Summary (MCS) scores in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Function assessment using SF-12, SF-6D R2 (cohort 1)	Utility Index (SF-6D R2) scores in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Function assessment using SF-12, SF-6D R2(cohort 2)	Utility Index (SF-6D R2) scores in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Pain Now (cohort 1)	Scores for Pain Now in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Pain Now (cohort 2)	Scores for Pain Now in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Usual level of Pain (cohort 1)	Scores for Usual level of Pain during the last week in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Usual level of Pain (cohort 2)	Scores for Usual level of Pain during the last week in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Best level of Pain (cohort 1)	Scores for Best level of Pain during the last week in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Best level of Pain (cohort 2)	Scores for Best level of Pain during the last week in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Worst level of Pain (cohort 1)	Scores for Worst level of Pain during the last week in subjects with SSGSV available	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Functional: Numerical rating scale for Pain, Worst level of Pain (cohort 2)	Scores for Worst level of Pain during the last week in subjects without available SSGSV	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Function: Six-minute walk test (cohort 1)	Six-minute walk test measurements in subjects with SSGSV available. The six-minute walk test was performed at a subset of clinical sites (for whom this test was standard of care) and was limited to patients for whom rest pain, wounds, or foot surgery (recent or anticipated) did not preclude weight bearing	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject
Function: Six-minute walk test (cohort 2)	Six-minute walk test measurements in subjects without available SSGSV. The six-minute walk test was performed at a subset of clinical sites (for whom this test was standard of care) and was limited to patients for whom rest pain, wounds, or foot surgery (recent or anticipated) did not preclude weight bearing	Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject

Collaborators and Investigators

• Sponsor: HealthCore-NERI
• Collaborators: Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI); W.L.Gore & Associates; Brigham and Women's Hospital; Boston Medical Center; Boston Scientific Corporation; Abbott; Cordis Corporation; Cardiovascular Systems Inc; Society for Vascular Surgery; Bard Ltd; Canadian Society for Vascular Surgery; Eastern Vascular Society; Midwest Vascular Society; New England Society for Vascular Surgery; Society for Clinical Vascular Surgery; Society for Interventional Radiology; Southern Vascular Society; Society for Vascular Medicine; Vascular and Endovascular Surgery Society; Vascular Interventional Advances; Western Vascular Society

Publications and helpful links

General Publications

• Menard MT, Farber A, Assmann SF, Choudhry NK, Conte MS, Creager MA, Dake MD, Jaff MR, Kaufman JA, Powell RJ, Reid DM, Siami FS, Sopko G, White CJ, Rosenfield K. Design and Rationale of the Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST-CLI) Trial. J Am Heart Assoc. 2016 Jul 8;5(7):e003219. doi: 10.1161/JAHA.116.003219.
• Farber A, Rosenfield K, Siami FS, Strong M, Menard M. The BEST-CLI trial is nearing the finish line and promises to be worth the wait. J Vasc Surg. 2019 Feb;69(2):470-481.e2. doi: 10.1016/j.jvs.2018.05.255.
• Powell R, Menard M, Farber A, Rosenfield K, Goodney P, Gray B, Lookstein R, Pena C, Schermerhorn M. Comparison of specialties participating in the BEST-CLI trial to specialists treating peripheral arterial disease nationally. J Vasc Surg. 2019 May;69(5):1505-1509. doi: 10.1016/j.jvs.2018.08.188.
• Rathakrishnan B, Secemsky EA. Turning the tide: Evolution of below-the-knee endovascular intervention. Vasc Med. 2021 Feb;26(1):26-27. doi: 10.1177/1358863X20978281. Epub 2020 Dec 14. No abstract available.
• Albaghdadi MS, Young MN, Chowdhury MM, Assmann S, Hamza T, Siami S, Villarreal M, Strong M, Menard M, Farber A, Rosenfield K. Clinical practice patterns and ascertainment bias for cardiovascular events in a randomized trial: A survey of investigators in the BEST-CLI trial. Vasc Med. 2021 Apr;26(2):180-186. doi: 10.1177/1358863X21995897.
• Farber A, Menard MT, Conte MS, Kaufman JA, Powell RJ, Choudhry NK, Hamza TH, Assmann SF, Creager MA, Cziraky MJ, Dake MD, Jaff MR, Reid D, Siami FS, Sopko G, White CJ, van Over M, Strong MB, Villarreal MF, McKean M, Azene E, Azarbal A, Barleben A, Chew DK, Clavijo LC, Douville Y, Findeiss L, Garg N, Gasper W, Giles KA, Goodney PP, Hawkins BM, Herman CR, Kalish JA, Koopmann MC, Laskowski IA, Mena-Hurtado C, Motaganahalli R, Rowe VL, Schanzer A, Schneider PA, Siracuse JJ, Venermo M, Rosenfield K; BEST-CLI Investigators. Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia. N Engl J Med. 2022 Dec 22;387(25):2305-2316. doi: 10.1056/NEJMoa2207899. Epub 2022 Nov 7.
• Siracuse JJ, Rowe VL, Menard MT, Rosenfield K, Conte MS, Powell R, Clavijo LC, Giles KA, Hamza TH, Van Over M, Cziraky M, White CJ, Strong MB, Farber A. Relationship between WIfI stage and quality of life at revascularization in the BEST-CLI trial. J Vasc Surg. 2023 Apr;77(4):1099-1106.e4. doi: 10.1016/j.jvs.2022.11.050. Epub 2022 Nov 23.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): March 1, 2022
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 11, 2014
• First Posted (Estimate): February 12, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: leg pain; Peripheral artery disease; claudication; Amputation; Critical limb ischemia; leg ulcer; gangrene; Surgical revascularization; Endovascular revascularization
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: BEST-CLI Trial; 1U01HL107407 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes