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The Impact of Diabetes on REvascularization (TIDE)

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ClinicalTrials.gov Identifier: NCT03085524
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : April 5, 2019
Sponsor:
Collaborators:
New England Research Institutes
Massachusetts General Hospital
Information provided by (Responsible Party):
Joshua Beckman, Vanderbilt University Medical Center

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.

Condition or disease Intervention/treatment
Peripheral Arterial Disease Diabetes Mellitus Diagnostic Test: Platelet function testing Diagnostic Test: Vascular ultrasonography

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.

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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Impact of Diabetes on REvascularization
Actual Study Start Date : August 1, 2017
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : August 31, 2020

Group/Cohort Intervention/treatment
Surgical Bypass
Subjects in the BEST-CLI trial assigned to surgical revascularization.
Diagnostic Test: Platelet function testing
The investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization

Diagnostic Test: Vascular ultrasonography
The investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year.

Endovascular
Subjects in the BEST-CLI trial assigned to endovascular revascularization.
Diagnostic Test: Platelet function testing
The investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization

Diagnostic Test: Vascular ultrasonography
The investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year.




Primary Outcome Measures :
  1. Major Adverse Limb Event - free survival [ Time Frame: 1 year ]
    The combination of amputation, surgical revascularization, thrombectomy, thrombosis, interposition graft, or death

  2. Restenosis [ Time Frame: 1 year ]
    Greater than 50% stenosis as determined by peak systolic velocity ratio of >2.4


Biospecimen Retention:   Samples With DNA
Leukoctyes


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Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03085524


Contacts
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Contact: Joshua A Beckman, MD 615-322-2318 joshua.a.beckman@vumc.org

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Sponsors and Collaborators
Vanderbilt University Medical Center
New England Research Institutes
Massachusetts General Hospital

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Responsible Party: Joshua Beckman, Professor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03085524     History of Changes
Other Study ID Numbers: 161402
First Posted: March 21, 2017    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The proposed research will include data from approximately 500 subjects enrolled in the BEST-CLI clinical trial. The final dataset will include self-reported demographic, ultrasonographic, and laboratoryl data from the subjects. The investigators will be collecting identifying information, but the final dataset will be stripped of identifiers prior to release for sharing. Thus, the investigators will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Diabetes Mellitus
Peripheral Arterial Disease
Peripheral Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases