Summary

for people ages 35 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

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.

Details

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.

Keywords

Peripheral Arterial Disease Diabetes Mellitus Peripheral Vascular Diseases Platelet function testing Vascular ultrasonography Surgical Bypass Endovascular

Eligibility

You can join if…

Open to people ages 35 years and up

  • 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-

You CAN'T join if...

  • 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

Locations

  • San Francisco VA Medical Center accepting new patients
    San Francisco California 94121 United States
  • University of California San Francisco Medical Center accepting new patients
    San Francisco California 94143 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Vanderbilt University Medical Center
ID
NCT03085524
Study Type
Observational
Last Updated
June 5, 2018