TIDE: The Impact of Diabetes on REvascularization

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03085524

Collaborator

HealthCore-NERI (Other), Massachusetts General Hospital (Other)

500

Enrollment

Locations

Anticipated Duration (Months)

11.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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	Phase
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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

The Impact of Diabetes on REvascularization

Actual Study Start Date :

Aug 1, 2017

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

Major Adverse Limb Event - free survival [1 year]
The combination of amputation, surgical revascularization, thrombectomy, thrombosis, interposition graft, or death
Restenosis [1 year]
Greater than 50% stenosis as determined by peak systolic velocity ratio of >2.4

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach VA Medical Center	Long Beach	California	United States	90822
2	Keck Medical Center of USC	Los Angeles	California	United States	90033
3	San Francisco VA Medical Center	San Francisco	California	United States	94121
4	University of California San Francisco Medical Center	San Francisco	California	United States	94143
5	University of Colorado Hospital	Aurora	Colorado	United States	80045
6	Yale New Haven Hospital	New Haven	Connecticut	United States	06510
7	University of Florida	Gainesville	Florida	United States	32610
8	Loyola University Medical Center	Chicago	Illinois	United States	60153
9	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
10	Iowa Heart Center	West Des Moines	Iowa	United States	50266
11	University Health System: LSU Health Sciences	Shreveport	Louisiana	United States	71103
12	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
13	Boston Medical Center	Boston	Massachusetts	United States	02118
14	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
15	Henry Ford Hospital	Detroit	Michigan	United States	48202
16	Michigan Vascular Center	Flint	Michigan	United States	48507
17	Michigan Heart - St. Joseph Mercy Health System	Ypsilanti	Michigan	United States	48197
18	University of Nebraska Medical Center	Omaha	Nebraska	United States	68106
19	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	Deborah Heart and Lung Center	Browns Mills	New Jersey	United States	08015
21	Rutgers University Hospital	Newark	New Jersey	United States	07103
22	New Mexico Heart Institute	Albuquerque	New Mexico	United States	87102
23	Albany Medical Center	Albany	New York	United States	12208
24	Mount Sinai Medical Center	New York	New York	United States	10029
25	Westchester Medical Center	Valhalla	New York	United States	10595
26	University of North Carolina Hospitals	Chapel Hill	North Carolina	United States	27599
27	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	28157
28	The Ohio State University	Columbus	Ohio	United States	43210
29	University of Toledo Medical Center	Toledo	Ohio	United States	43604
30	Oregon Health and Science University	Portland	Oregon	United States	97204
31	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
32	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
33	University of Virginia	Charlottesville	Virginia	United States	22908
34	Inova Heart and Vascular Institute	Falls Church	Virginia	United States	22042
35	Harborview Medical Center	Seattle	Washington	United States	98104
36	Benaroya Research Institute at Virginia Mason	Seattle	Washington	United States	98122
37	Gunderson Health System	La Crosse	Wisconsin	United States	54601
38	University of Wisconsin - Madison	Madison	Wisconsin	United States	53706
39	St. Boniface General Hospital	Winnipeg	Manitoba	Canada	R2H 2A6
40	The Ottawa Hospital	Ottawa	Ontario	Canada	K1Y 4E9
41	Sunnybrook Health Sciences	Toronto	Ontario	Canada	M4N 3M5
42	Chu de Quebec, St-Francois d'Assise Hospital	Québec	Quebec	Canada	G1L 3P7
43	Helsinki University Hospital	Helsinki		Finland	00029

Sponsors and Collaborators

Vanderbilt University Medical Center
HealthCore-NERI
Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Joshua Beckman, Professor, Vanderbilt University Medical Center

ClinicalTrials.gov Identifier:

NCT03085524

Other Study ID Numbers:

161402

First Posted:

Mar 21, 2017

Last Update Posted:

Sep 2, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Peripheral Arterial Disease

Peripheral Vascular Diseases

Diabetes Mellitus

Study Results

No Results Posted as of Sep 2, 2021