Title: Diagnostic tools to establish the presence and severity of peripheral arterial disease in people with diabetes
Funder: Department of Health and Social Care

Abstract: THE PROBLEM_x000D_ In the United Kingdom (UK), there are over 7,000 leg amputations each year because of diabetes. More than 4 out of 5 amputations take place because a foot wound (an ulcer) does not heal. The most important cause of this is poor blood circulation to the feet. The detection of poor circulation in patients with diabetes is difficult. A number of tests exist to detect poor circulation. However, there is confusion as to which is the best test. This may result in missed diagnoses of poor circulation leading to amputation and even death. Hence, we propose to carry out a study to determine which test is best._x000D_ _x000D_ THE STUDY_x000D_ We will ask adult patients with diabetes to take part in the study. The study will take place in 18 centres across the UK. Patients from both primary care (general practice & community clinics) and hospital settings will be invited. Patients will be asked to attend two study visits. At the first visit, which will take 40 minutes and coincide with a routine appointment, patients will undergo five bedside tests:_x000D_ _x000D_ •Blood pressure at the ankle (called ankle-brachial pressure index or ABPI)_x000D_ •Blood pressure at the ankle after doing heal raises (called exercise ABPI)_x000D_ •Blood pressure at the big toe (called toe-brachial pressure index or TBPI)_x000D_ •Visible blood flow waveform (called Doppler)- this involves gently applying a small device and gel on the skin at the ankle. _x000D_ •Audible blood flow waveforms (called Doppler)- this also involves gently applying a small device and gel on the skin at the ankle. _x000D_ _x000D_ In some centres we will also test the performance of an additional sixth test. We have developed this test and studied its performance in a study of 305 patients. In this study we found that the new test was very accurate. It consists of an ultrasound test at the ankle, using a sensor and gel on the skin. These ultrasound machines are moderately costly. Therefore, we will limit this test to only 4 centres to increase our understanding of this technique._x000D_ _x000D_ The second visit will take place within 2-weeks of the first visit. In the second visit, which will take 30-minutes, patients will have a more detailed scan of their blood vessels in their leg using a computed tomography angiography (CTA) or magnetic resonance angiography (MRA) scan. The results from the bedside tests will be compared to the results of the CTA or MRA to identify the most accurate test. _x000D_ _x000D_ IMPACT OF OUR RESEARCH_x000D_ This research should improve the detection of poor circulation in patients with diabetes and reduce the number of amputations and deaths. The results will be published in scientific journals, patient forums and news outlets. _x000D_ _x000D_ PATIENTS AND PUBLIC INVOLVEMENT_x000D_ We have designed this study with the input from patients who were part of a similar study and an online survey of patients from the wider diabetic community. Some of these patients also took part in a focus group, led by our patient representative.

Lay abstract: BACKGROUND_x000D_ Peripheral arterial disease is a risk factor for cardiovascular disease, foot ulceration and limb amputation in diabetic patients. Diagnosis enables optimisation of therapies to manage these risks. Its diagnosis is fundamental though challenging. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most useful._x000D_ _x000D_ AIM_x000D_ To determine the diagnostic performance of index tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of peripheral arterial disease (PAD) in patients with diabetes as determined by a reference test (CTA or MRA). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan), which has shown promising results in a recent study (1)._x000D_ _x000D_ METHODS_x000D_ A prospective multicentre diagnostic accuracy study. We aim to recruit 730 patients with diabetes from 18 centres covering primary (general practice & community clinics) and secondary (inpatient & outpatient) care. Participants will be identified and contacted prior to their routine clinic visit at which point they will be consented and undergo index tests. Tests will be performed in a logical sequence to reduce the risk of bias. Performance of index tests will be based on prespecified diagnostic thresholds for PAD._x000D_ Reference tests (CTA/MRA) will be performed according to a standardised protocol within 2-weeks of the index tests. Imaging will be reported locally at the recruiting centre and centrally by blinded consultant radiologists at our core lab using a validated angiographic scoring system (ANGIO score), which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ?50% stenosis, or tandem lesions with a combined value of ?50%, will be used as the threshold for the diagnosis of PAD. _x000D_ The primary outcome measure of diagnostic performance will be test sensitivity. Statistical analysis and oversight of data will be performed by the ECTU. _x000D_ _x000D_ TIMELINE_x000D_ Study setup (6 months), recruitment (12 months) and study closeout (6 months). _x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION _x000D_ Improved detection of PAD will result in improved patient care, including a reduction in lower limb amputation and cardiovascular mortality in patients with diabetes. The final results will be published in a high impact journal and presented at scientific conferences and patient groups. A lay video summary of results will be circulated to participants and patients. _x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT_x000D_ We have designed this study with the help of feedback from patients who were part of a similar study and a survey of patients from the wider diabetic community. Some of these patients also took part in a focus group, led by our patient representative.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR;METABOLIC AND ENDOCRINE