The Impact of Diabetes on REvascularization

Diabetes Mellitus Clinical Trial

— TIDE  

Official title:

The Impact of Diabetes on REvascularization

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03085524
• Other study ID #: 161402
• Status: Active, not recruiting
• Start date: August 1, 2017
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Diagnostic Test:
• Platelet function testing
The investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization
• Vascular ultrasonography
The investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	Carelon Research, Massachusetts General Hospital

Countries where clinical trial is conducted

United States,  Canada,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Adverse Limb Event - free survival	The combination of amputation, surgical revascularization, thrombectomy, thrombosis, interposition graft, or death	1 year
Primary	Restenosis	Greater than 50% stenosis as determined by peak systolic velocity ratio of >2.4	1 year