Peripheral Arterial DiseaseTIDENCT03085524
The Impact of Diabetes on REvascularization
An observational study of Peripheral Arterial Disease and Diabetes Mellitus, run by Vanderbilt University Medical Center at 43 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Peripheral Arterial Disease, Diabetes Mellitus
- What is being tested?
- Platelet function testing and Vascular ultrasonography
- How many people
- 215 participants
- Where
- 43 sitesin 3 countries
- Study dates
- 1 Aug 2017to 1 Oct 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 9Show fewer
- 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-
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
43 sites in 3 countries.
43 sites in 3 countries
United States38 sites
Albany Medical Center
Albany, New York, 12208
New Mexico Heart Institute
Albuquerque, New Mexico, 87102
University of Colorado Hospital
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Boston Medical Center
Boston, Massachusetts, 02118
Deborah Heart and Lung Center
Browns Mills, New Jersey, 08015
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27599
University of Virginia
Charlottesville, Virginia, 22908
Loyola University Medical Center
Chicago, Illinois, 60153
The Ohio State University
Columbus, Ohio, 43210
Decatur Memorial Hospital
Decatur, Illinois, 62526
Henry Ford Hospital
Detroit, Michigan, 48202
Inova Heart and Vascular Institute
Falls Church, Virginia, 22042
Michigan Vascular Center
Flint, Michigan, 48507
University of Florida
Gainesville, Florida, 32610
Greenville Memorial Hospital
Greenville, South Carolina, 29605
Gunderson Health System
La Crosse, Wisconsin, 54601
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Long Beach VA Medical Center
Long Beach, California, 90822
Keck Medical Center of USC
Los Angeles, California, 90033
University of Wisconsin - Madison
Madison, Wisconsin, 53706
Yale New Haven Hospital
New Haven, Connecticut, 06510
Mount Sinai Medical Center
New York, New York, 10029
Rutgers University Hospital
Newark, New Jersey, 07103
University of Nebraska Medical Center
Omaha, Nebraska, 68106
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science University
Portland, Oregon, 97204
San Francisco VA Medical Center
San Francisco, California, 94121
University of California San Francisco Medical Center
San Francisco, California, 94143
Harborview Medical Center
Seattle, Washington, 98104
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98122
University Health System: LSU Health Sciences
Shreveport, Louisiana, 71103
University of Toledo Medical Center
Toledo, Ohio, 43604
Westchester Medical Center
Valhalla, New York, 10595
Iowa Heart Center
West Des Moines, Iowa, 50266
Wake Forest Baptist Health
Winston-Salem, North Carolina, 28157
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
Michigan Heart - St. Joseph Mercy Health System
Ypsilanti, Michigan, 48197
Canada4 sites
The Ottawa Hospital
Ottawa, Ontario, K1Y 4E9
Chu de Quebec, St-Francois d'Assise Hospital
Québec, Quebec, G1L 3P7
Sunnybrook Health Sciences
Toronto, Ontario, M4N 3M5
St. Boniface General Hospital
Winnipeg, Manitoba, R2H 2A6
About this study
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.
Read the 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.
- Conditions
- Peripheral Arterial Disease, Diabetes Mellitus
- Being tested
- Platelet function testing, Vascular ultrasonography
- Medical subject headings
- Peripheral Arterial Disease, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platelet function testingDiagnostic test
The investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization
Vascular ultrasonographyDiagnostic test
The investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year.
| Study group | Role | What they receive |
|---|---|---|
| Surgical Bypass | Subjects in the BEST-CLI trial assigned to surgical revascularization. Receives: Diagnostic Test: Platelet function testing; Diagnostic Test: Vascular ultrasonography | |
| Endovascular | Subjects in the BEST-CLI trial assigned to endovascular revascularization. Receives: Diagnostic Test: Platelet function testing; Diagnostic Test: Vascular ultrasonography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Adverse Limb Event - free survival
The combination of amputation, surgical revascularization, thrombectomy, thrombosis, interposition graft, or death
Measured: 1 year
Restenosis
Greater than 50% stenosis as determined by peak systolic velocity ratio of >2.4
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2017
- Study start1 Aug 2017
- Primary completion1 Oct 2021
- Study completion1 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 215 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Carelon Research, Massachusetts General Hospital
- Responsible party
- Principal investigator, Joshua Beckman, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03085524
- Sponsor's protocol ID
- 161402
- Acronym
- TIDE
- Status last verified
- Jul 2024
- First submitted
- 14 Mar 2017
- Last updated
- 8 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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 laboratory 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.
Publications
Sullivan AE, Huang S, Kundu S, Thomas VE, Clair DG, Aday AW, Menard MT, Farber A, Rosenfield K, Newman JD, Berger JS, Wells QS, Freiberg MS, Linton MF, Beckman JA. Association of Lipoprotein(a) With Major Adverse Limb Events and All-Cause Mortality Following Revascularization for Chronic Limb-Threatening Ischemia: A Substudy of the BEST-CLI Trial. J Am Heart Assoc. 2025 Jun 3;14(11):e041177. doi: 10.1161/JAHA.125.041177. Epub 2025 May 22.
PubMed 40401600
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Diabetes on REvascularization
- ClinicalTrials.gov ID
- NCT03085524
- Acronym / sponsor ID
- TIDE / 161402
- Conditions
- Peripheral Arterial Disease, Diabetes Mellitus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Carelon Research, Massachusetts General Hospital
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 21 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Surgical Bypass | – | Diagnostic Test: Platelet function testing, Diagnostic Test: Vascular ultrasonographySubjects in the BEST-CLI trial assigned to surgical revascularization. |
| Endovascular | – | Diagnostic Test: Platelet function testing, Diagnostic Test: Vascular ultrasonographySubjects in the BEST-CLI trial assigned to endovascular revascularization. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Platelet function testingThe investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization | Diagnostic test | Endovascular, Surgical Bypass |
| Vascular ultrasonographyThe investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year. | Diagnostic test | Endovascular, Surgical Bypass |
Primary outcome
Major Adverse Limb Event - free survival
Time frame: 1 year
The combination of amputation, surgical revascularization, thrombectomy, thrombosis, interposition graft, or death
Restenosis
Time frame: 1 year
Greater than 50% stenosis as determined by peak systolic velocity ratio of >2.4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
- Derived from this study: PubMed 40401600Sullivan AE, Huang S, Kundu S, Thomas VE, Clair DG, Aday AW, Menard MT, Farber A, Rosenfield K, Newman JD, Berger JS, Wells QS, Freiberg MS, Linton MF, Beckman JA. Association of Lipoprotein(a) With Major Adverse Limb Events and All-Cause Mortality Following Revascularization for Chronic Limb-Threatening Ischemia: A Substudy of the BEST-CLI Trial. J Am Heart Assoc. 2025 Jun 3;14(11):e041177. doi: 10.1161/JAHA.125.041177. Epub 2025 May 22.
- Individual participant dataSharing planned: No. 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 laboratory 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
43 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Peripheral Arterial Disease and Diabetes Mellitus, run by Vanderbilt University Medical Center at 43 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Canada, Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Adverse Limb Event - free survival (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03085524, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2024.