Clinical trial NCT03085524: The Impact of Diabetes on REvascularization
Official title: The Impact of Diabetes on REvascularization
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Peripheral Arterial Disease
Diabetes Mellitus
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Carelon Research
name: Massachusetts General Hospital
First posted: 2017-03-21
Enrollment: 215
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This ancillary study is an observational study design examining the effects of diabetes mellitus on restenosis following surgical or endovascular revascularization in CLI patients. Eligible patients will be screened according to the specified exclusion and inclusion criteria of the BEST-CLI trial.

Brief summary: The presence of foot symptoms at rest or tissue necrosis in patients with peripheral artery disease is a medical urgency and represents a state of critical limb ischemia (CLI) where the risk of amputation, in the absence of revascularization, is high. No trial conducted to date in peripheral revascularization has determined the effect of diabetes on mechanism of revascularization failure. Therefore, this trial represents a unique opportunity to investigate the mechanisms by which diabetes affects surgical and endovascular revascularization procedures with the long-term goal of improving outcomes in CLI.

Detailed description: Peripheral artery disease is a condition defined by marked accumulation of atherosclerotic plaque below the distal aorta that reduces lower limb arterial perfusion. Blood flow reductions may be inadequate for exercising limbs and cause ischemic muscle pain, called intermitted claudication, or, in severe cases, the reduction may be inadequate for basal metabolism and cause pain at rest, ulceration, or gangrene. The presence of symptoms at rest or tissue necrosis is a medical urgency and represents a state of critical limb ischemia (CLI) where the risk of amputation, in the absence of revascularization, is high. The ageing of the population and the increasing prevalence of diabetes mellitus ensures this population will continue to grow in the foreseeable future. The impact of diabetes, however, is not limited to PAD incidence. Diabetic patients represent a particularly vulnerable subset of PAD patients and have a four-fold risk of CLI compared to non-diabetic patients. Indeed, in previous studies of CLI, more than half of patients have diabetes. As a result, the combination of diabetes and PAD accounts for more than half of non-traumatic amputations in the United States. Diabetic patients often present with foot ulcerations as their first manifestation of PAD and have challenging anatomy for revascularization. Failed vascular reconstructions, both endovascular or surgical, often result in additional tissue loss and transtibial amputations. Despite these challenges, the mechanisms of restenosis and the impact of diabetes have not been well explored for both types of revascularization in patients with CLI. The BEST-CLI trial is a multi-center, randomized, comparative effectiveness trial comparing open surgical bypass therapy to endovascular therapy in CLI patients with a composite clinical endpoint denoted as Major Adverse Limb Event free survival (MALE-free survival). However, the BEST-CLI trial does not study the mechanisms by which revascularization may fail. This proposal will extend the novel clinical work of the BEST-CLI trial by studying the mechanisms of bypass vein graft and stent failure. The investigators will adjudicate the mode of revascularization (vein graft or stent) in a central core laboratory, measure systemic markers of diabetic dysmetabolism including inflammation, insulin resistance, adverse adipokine expression, poor nutrition, and renal dysfunction, and begin to study the association of these factors with graft failure. Indeed, no trial conducted to date in either coronary or peripheral revascularization has determined the mechanism of revascularization failure, the impact of diabetes, nor the relationship between conduit patency and clinical outcomes. Therefore, this trial represents a unique opportunity to investigate the mechanisms by which diabetes affects surgical and endovascular revascularization procedures.

Eligibility criteria: Inclusion Criteria:

* Male or female, age 35 years or older
* Atherosclerotic, infrainguinal PAD
* CLI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain, consistent with Rutherford classes 4-6
* Candidate for either open or endovascular infrainguinal revascularization as judged by the treating investigators
* Adequate inflow into the index femoral artery
* Adequate popliteal, tibial, or pedal revascularization target
* Willing to comply with protocol, attend follow-up appointments, complete all study assessments, and provide informed consent
* Endovascular revascularization with a stent
* Surgical revascularization with a vein graft-

Exclusion Criteria:

* Femoropopliteal disease pattern consistent with TASC IIA
* Complete occlusion of the iliac artery
* Aortoiliac occlusive disease or severe common femoral artery disease
* Presence of a femoral, popliteal or tibial aneurysm of the index limb
* Life expectancy less than 2 years
* Deemed excessive risk for surgical bypass
* A vascular disease prognosis that includes an anticipated above ankle amputation on index limb within 4 weeks of index procedure
* Renal dysfunction defined as MDRD eGFR ≤ 30ml/min/173 m2 at the time of screening
* Currently on dialysis or history of a renal transplant
* A documented hypercoagulable state
* Nonatherosclerotic occlusive disease
* Any prior infrainguinal revascularization
* Current immuno-suppressive medication, chemotherapy or radiation therapy
* Absolute contraindication to iodinated contrast

Primary outcomes:
measure: Major Adverse Limb Event - free survival
timeFrame: 1 year
measure: Restenosis
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach VA Medical Center
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Shreveport
country: United States
facility: University Health System: LSU Health Sciences
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: Michigan Vascular Center
state: Michigan
city: Ypsilanti
country: United States
facility: Michigan Heart - St. Joseph Mercy Health System
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Newark
country: United States
facility: Rutgers University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Memorial Hospital
state: South Carolina
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: La Crosse
country: United States
facility: Gunderson Health System
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences
state: Ontario
city: Québec
country: Canada
facility: Chu de Quebec, St-Francois d'Assise Hospital
state: Quebec
city: Helsinki
country: Finland
facility: Helsinki University Hospital
Study officials:
References: