The F.L.I.G.H.T. (Fluorescence Image-Guided Healing Trial) for Diabetic Foot Ulcers: A Phase IV Trial

Wound care is a major clinical challenge and presents an enormous burden to health care worldwide. Wounds Canada describes chronic wounds as "a Canadian healthcare crisis." According to Wounds Canada and Diabetes Canada, approximately 15% of the 2.3 million diabetic Canadians will develop a diabetic foot ulcer (DFU) and every 30 seconds someone in the world loses a toe or limb to diabetes. Diabetics are about 23x more likely to be hospitalized for amputations, approximately 85% of which are due to a previous DFU. Delayed wound healing has been linked to a variety of factors including infection, which disrupts key biological changes at the tissue and cellular level that are associated with the wound healing process. Standard of care (SoC) of DFU infections involves visual inspection of the wound under white light (WL) and identification of common signs of infection using the Clinical Signs and Symptoms Checklist. However, SoC is limited by inconsistent guidelines and subjective assessment. In addition, visual inspection and WL-guided sampling are inaccurate and currently, no point-of-care technologies exist to assist the unaided eye. In response to this gap, Dr. DaCosta (PI) and colleagues at University Health Network developed a handheld fluorescence imaging platform (MolecuLight i:X) that detects bacterial autofluorescence in wounds in real-time, at the point-of-care, and without the use of exogenous contrast agents. The investigators propose a 3-year randomized control trial to test the therapeutic benefit of AF-image guided intervention on DFU management using the i:X. The research questions are Q1). Does AF-guided diagnosis and wound bed preparation improve wound healing in DFUs relative to SoC alone? Q2). Does AF-guided intervention decrease the bioburden in DFUs relative to SoC alone? Q3). Does AF-guided intervention improve patient quality of life relative to SoC alone? Q4). Is AF-guided intervention associated with reduced treatment cost? Primary objective: is to determine if AF-guided diagnosis and wound bed preparation improve wound healing in DFUs compared to SoC alone. To measure this, the investigators will compare between study arms i) the frequency of complete wound healing (CWH) at 12 weeks; ii) the frequency of partial wound healing (PWH) at 6 and 12 weeks, CWH at 6 weeks, and mean time-to-CWH (days); iii) the reduction in wound size at 12 weeks; and iv) the rate of wound healing over 12 weeks. Secondary objective: is to determine if AF-guided intervention decreases the bioburden in DFUs compared to SoC alone by evaluating bacterial diversity and measuring bacteria load at specified regular intervals over 12 weeks. Tertiary objective: is to determine if AF-guided intervention is associated with improved quality of life (QoL) and with reduced treatment costs, which will be measured by using patient questionnaires and the Canadian Institute for Health Information database.

If successful, this Randomized Control Trial (RCT) will demonstrate that AF image-guided wound care improves time to CWH or PWH among Ontarians with DFUs by increasing wound healing rates and reducing bioburden. If our technology can improve CWH by our target of >= 16% (absolute), an additional 55,000 Canadians could reach CWH by 12 weeks, resulting in reduced wound care costs and improved QoL. The average cost of treating a DFU is $5000-8000/patient. Improving the number of patients that achieve CWH by >= 16% will substantially reduce costs associated with treating DFUs in Canada. The results of this study may inform health policy decisions and recommendations for changes to current SoC DFU practice guidelines. Health economic and QoL comparison of AF-guided wound care vs SoC in the proposed RCT will help define the overall value proposition of the new approach. If the investigators fail to demonstrate improved wound healing rates, this will also be of value to physicians, patients and the Canadian health care system. Knowing not to further pursue this line of research is important in an era of limited funding.