Pilot Study to Determine Percent Tissue Perfusion and Cellular Viability Using SPY Imaging

Study Overview
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Brief Summary
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Little is known about chronic wound microenvironments, especially in peripheral vascular disease (PVD) and diabetic patients. At the demarcation line, the percentage of viable cells and tissue is unclear. A means to determine cell viability, particularly discerning an apoptotic or necrotic cell pathway would indicate where the line of demarcation should be drawn. The information generated would better predict clinical outcome using SPY Imaging. Cellular studies are needed to successfully confirm a clear line of demarcation to eliminate surgeon subjectivity.

Detailed Description
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Peripheral arterial disease (PAD), like other more central macrovascular diseases, is common in diabetes. PAD can lead to critical limb ischemia, either alone or when combined with an injury like a foot ulcer. The diabetic foot ulceration requires adequate circulation to heal; if the circulation is impaired such that the tissue oxygen demand exceeds supply, critical limb ischemia ensues, placing the limb at risk. Most often, patients with critical limb ischemia, undergo multiple debridements in the operating room as well as vascular procedures, prior to reaching a viable level of amputation. This increases the patients' co-morbidities from repetitive exposure to anesthesia. Each debridement may be removing viable tissue and decreasing the length of the eventual amputation. Additionally, intraoperatively, the viability of the skin edges is a subjective assessment based on the surgeon's experience. That judgement can be inaccurate in 10-20% of cases and lad to reoperation. With the use of the SPY imaging system, a better assessment of not only macrovascularity, but also microvascularity of the tissues is able to be evaluated objectively. This helps identify the tissues that are underperfused. The investigators are unaware of any literature evaluating the use of SPY imaging in the lower extremities intraoperatively during amputations or debridements. There are many studies published for the use of this technology during ophthalmic procedures , cerebral aneurismal repair, cardiac surgery and breast reconstruction. In cardiac surgery, the use of ICG based imaging has proven to be helpful in assessing the quality of bypass grafts and eliminating the need for radiography or catheter insertion (Reuthebuch et al., 2004). In ophthalmic procedures, ICG angiography has been fundamental in identifying many microvascular pathologies (Slakter, Yannuzzi, Guyer, Sorenson, & Orlock, 1995). Furthermore, neurosurgeons have found that the use of ICG angiography is far more superior than DS angiography in identifying small vessels . As it has already been proven to be a good adjunct intraoperatively to visualize microvasculature, the investigators would like to apply this to the lower extremities. Identifying underperfused tissues intraoperatively can help the surgeon objectively decide an appropriate level of amputation/debridement to effectively minimize the number of revisional surgeries. Also, there are no studies that comprehensively evaluate and compare the effectiveness of other modalities that also attempt to assess vascularity with the SPY imaging system. The information gained could be pivotal and help to gain more insight in patients with difficult to heal wounds, especially in the presence of PVD.

Official Title
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Pilot Study for: Eye vs. Spy - A Prospective, Randomized Study Evaluating Patient Outcomes With the Use of SPY Imaging During Amputations or Debridements

Conditions
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Peripheral Vascular Disease

Intervention / Treatment
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* Device: SPY Imaging, ICG dye (0.2 - 0.5 mg/kg)
* Device: SPY Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18 years or older. Subject has PVD demonstrated by angiogram. Subject is undergoing the first amputation/debridement after vascular intervention, if intervention is/was warranted. Subject has had a vascular consult and/or intervention. Subject must sign an IRB approved informed consent. Subject is willing and able to complete required follow up. Exclusion Criteria: Subject has no evidence of PVD Subject's wound presents with a malignancy in the wound bed. Subject has liver disease (Previously diagnosed with liver disease or elevated AST, ALT, Alk Phos, or Bilirubin labs within 30 days of procedure). Subject has a disorder or situation that the investigator believes will interfere with study compliance.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPY Imaging<br>SPY Imaging Prior to Amputation or Debridements (50 participants) | Device: SPY Imaging, ICG dye (0.2 - 0.5 mg/kg)<br>* Intravenous(1X) in conjunction with SPY Imaging (1 arm)<br>* Other names: Indocyanine Green, IC-GREEN;Device: SPY Imaging<br>* SPY Imaging to assess tissue perfusion<br>|
| No Intervention: No SPY Imaging<br>Amputation or Debridements as Standard of Care (50 participants) | |
| Experimental: Validation Against Angiogram<br>Patients who are scheduled to undergo an angiogram will also receive ICG angiography (SPY). This will occur at specific time points: 1.) before the angiogram/intervention is performed 2.) immediately after the angiogram/intervention is performed 3.) 5-7 days after angiogram/intervention 4.) 21-30 days after angiogram/intervention. (30 participants) | Device: SPY Imaging, ICG dye (0.2 - 0.5 mg/kg)<br>* Intravenous(1X) in conjunction with SPY Imaging (1 arm)<br>* Other names: Indocyanine Green, IC-GREEN;Device: SPY Imaging<br>* SPY Imaging to assess tissue perfusion<br>|
| Experimental: Establishing Normal Values<br>To establish baseline lower extremity perfusion in non-PVD patients. Patients requiring an angiogram for other vascular processes unrelated to the lower extremity will be recruited into this study. ICG angiography (SPY) of the lower extremity will be performed at the time of the angiogram. (30 Participants) | Device: SPY Imaging, ICG dye (0.2 - 0.5 mg/kg)<br>* Intravenous(1X) in conjunction with SPY Imaging (1 arm)<br>* Other names: Indocyanine Green, IC-GREEN;Device: SPY Imaging<br>* SPY Imaging to assess tissue perfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of percent cellular viability | Determine percent cellular viability (vs. apoptotic/dead) of cells at demarcation line | 6 weeks | 
| Rate of infection, dehiscence and re-amputation | Rate of infection, dehiscence and re-amputation in patients undergoing SPY imaging | 20 weeks | 
| Number of debridements, revisional surgeries and days of stay in hospital | The endpoint for evaluation will be the number of revisional surgeries and number of days of stay in hospital within 20 weeks of the first procedure. | 20 weeks |