The use of different diagnostic tests for the detection of poor circulation in people with diabetes
| ISRCTN | ISRCTN12358788 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12358788 |
| IRAS number | 301408 |
| ClinicalTrials.gov number | NCT05009602 |
| Secondary identifying numbers | CPMS 50623, NIHR131855, IRAS 301408 |
- Submission date
- 15/10/2021
- Registration date
- 18/10/2021
- Last edited
- 11/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Diabetes is a lifelong condition that causes a person's blood sugar level to become too high. In people with diabetes, if high blood glucose levels are experienced over a period of years, blood vessels can become damaged which can lead to plaque forming in the blood vessels, rendering them unable to deliver enough blood to neighbouring cells. Poor blood circulation can lead to a higher chance of developing serious foot problems. In the UK there are over 7,000 leg amputations each year because of diabetes. The most important cause of this is poor circulation. 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. The aim of this study is to determine which test is best.
Who can participate?
Adult patients with diabetes
What does the study involve?
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 tests:
1. Blood pressure at the ankle (called ankle-brachial pressure index or ABPI)
2. Blood pressure at the ankle after doing heal raises (called exercise ABPI)
3. Blood pressure at the big toe (called toe-brachial pressure index or TBPI)
4. Visible blood flow waveform (called Doppler)
5. Audible blood flow waveforms (called Doppler)
In some centres the researchers will also test the performance of an additional sixth test. They have developed this test and studied its performance in a study of 305 patients. It consists of an ultrasound test at the ankle, using a sensor and gel on the skin.
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 the 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.
What are the possible benefits and risks of participating?
Participants will undergo comprehensive testing and imaging for peripheral arterial disease (poor circulation) as part of this study. If previously undiagnosed, the diagnosis of peripheral arterial disease may prompt their doctor to initiate medicines that will help reduce their chance of having a stroke, heart attack and worsening of their peripheral arterial disease.
Additionally, if participants are diagnosed as having peripheral arterial disease, they may be eligible for additional measures to reduce the risk of developing a foot ulcer. These additional measures may include more frequent foot checks or new footwear.
If participants have an active ulcer, a diagnosis of peripheral arterial disease will trigger a specialist review by a vascular surgeon for consideration of timely revascularisation to improve the chance of ulcer healing and reduce the risk of amputation.
Participants may have a Computed Tomography Angiography (CTA) procedure, which, for the majority of participants (about 80%), will be added to the procedures they would have if they did not take part. This procedure uses ionising radiation to form images of the body and provide the doctor with other clinical information. Ionising radiation may cause cancer many years or decades after the exposure. We are all at risk of developing cancer during our lifetime. 50% of the population is likely to develop one of the many forms of cancer at some stage during our lifetime. Taking part in this study may increase the chances of this happening to you to about 0.12% or 1 in 800.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
September 2021 to February 2024
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Laura Burgess, l.burgess@imperial.ac.uk
Contact information
Scientific
Imperial College London
Section of Vascular Surgery
Room 14, 4th Floor East Wing
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
| Phone | +44 (0)7928785395 |
|---|---|
| l.burgess@imperial.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Diagnostic tools to establish the presence and severity of peripheral arterial disease in people with diabetes |
| Study acronym | DM PAD 1.1 |
| Study objectives | To determine the diagnostic performance of index tests (audible handheld Doppler, visual handheld Doppler, 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). |
| Ethics approval(s) | Approved 12/10/2021, London Central REC (3rd Floor, Barlow House, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)207 104 8225; londoncentral.rec@hra.nhs.uk), REC ref: 21/PR/1221 |
| Health condition(s) or problem(s) studied | Peripheral arterial disease in people with diabetes |
| Intervention | VISIT 0 (REMOTE SCREENING) To minimise patient burden, the researchers have adopted a remote screening process and incorporated the index tests into a routine visit episode to reduce the number of additional visits to one. Patients will be remotely screened at least 72 hours prior to their routine visit by their clinical team. If eligible for recruitment, they will be contacted by phone regarding the study. The study will be explained and if the patient gives verbal consent to receiving study information material, then these will be emailed or posted to the patient for consideration. They will be told that formal consent will be taken at visit 1 if they agree to partake in the study and that if they choose not to then this wouldn’t affect their usual clinical care. VISIT 1 (INDEX TESTS) Visit 1 will occur at a planned/ routine visit i.e., this would have occurred regardless of whether the patient was recruited onto the study or not. Patients will undergo routine assessment and care by the local clinical team. There is some overlap regarding tasks that would be performed as part of routine/usual care and as part of the study. Such tasks will be highlighted as 'ROUTINE' when describing the order of events below. A routine visit usually lasts 30 minutes. The researchers expect that the study will add 40 minutes to the usual episode. The researchers are primarily evaluating five index tests across all research centres; ABPI, expertise ABPI, TBPI, visual handheld Doppler and audible handheld Doppler. However, in four centres, they will evaluate the PAD scan as a sixth test. They have chosen not to evaluate this test at all centres as DUS machines are moderately costly and not currently available at every site. Index tests will be performed by a member of the local clinical team. Tests will be performed on one limb only; the most problematic side in symptomatic patients or randomly selected side in asymptomatic patients. Index tests will be performed in a predetermined order to minimise influence carrying over from one test to the other. Audible and visual handheld Doppler involve semi-objective interpretation of arterial waveforms and therefore could be influenced by knowledge of the tests with an objective output (TBPI, ABPI and exercise ABPI. Therefore, semi-objective tests will be performed first followed by objective tests Order of events at visit 1: - Eligibility check; 5 min - Recording of demographic details and medical history; 5 min - Assessment for neuropathy (ROUTINE); 5 min - Assessment of diabetic foot ulcer severity, if relevant (ROUTINE); 5 min - Index tests for the diagnosis of peripheral arterial disease: 1. Audible handheld Doppler (ROUTINE); 5 min 2a. Visual handheld Doppler; 5 min 2b. PAD-scan (in 4 selected centres); 5 min *N.B the order of 2a. and 2b. will be randomised* 3. ABPI (ROUTINE); 5 min 4. TBPI; 5 min 5. Exercise ABPI i.e., ABPI performed following repetitive heal raising; 5 min - Patient acceptability; patients will be asked to rate their experience of each test on a Likert scale - Blood test to assess renal function (ROUTINE in a proportion of patients); 5 min - Repeating of index tests (only performed in the first 100 volunteering patients); 40 min The first 100 volunteering patients will have all index tests repeated (in the same leg) on the same day, by the same operator and also by an alternative operator to assess the inter- and intra-rater reliability. VISIT 2 (REFERENCE TEST) - MRI or CTA; 30 min The reference test will be performed within 2 weeks of the index tests. The final decision regarding whether the patient undergoes CTA or MRA will depend on local protocol and patient choice. A proportion of patients would undergo a CTA or MRA regardless of whether they were taking part in the trial or not. FOLLOW UP Patients will be followed up 12 months from the time of the index tests. Follow up will be performed by review of the clinical notes. The purpose of follow up will be to ascertain whether the index tests can be used to predict ulcer healing, ulcer recurrence, revascularisation, amputation, cardiovascular events and mortality. RECRUITMENT OF INPATIENTS The above description is relevant to the recruitment of patients from clinics. The researchers will also be recruiting patients admitted for hospital care. Patients admitted for inpatient hospital care will be first identified by the inpatient podiatry, vascular or diabetes teams. Patients will have at least 24 hours to consider the patient information material. Participating patients will have index tests performed at their bedside. Where possible, the reference test will be performed during their inpatient stay to avoid additional hospital visits. |
| Intervention type | Other |
| Primary outcome measure | Diagnostic accuracy of the PAD scan and the other bedside tests for the diagnosis of peripheral arterial disease will be compared to the results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) (reference test) at 2 weeks |
| Secondary outcome measures | 1. Health economic outcome - the cost of the test, including direct costs and amortisation of capital equipment and use of other healthcare resources for prevention and treatment of the disease over a time horizon of 5 years 2. Health economic outcome - incremental cost-effectiveness ratio at 5 years 3. Health economic outcome - Quality Adjusted Life Years at 5 years 4. Specificity of index tests, comparing index tests to reference tests at 2 weeks 5. Likelihood ratios of index tests, comparing index tests to reference tests at 2 weeks 6. Predictive values of index tests, comparing index tests to reference tests at 2 weeks 7. Diagnostic odds ratio of index tests, comparing index tests to reference tests at 2 weeks 8. Patient acceptability of each index test, measured on a Likert scale following the completion of the tests at visit 1 9. Technical success including inability to perform, refusal and discontinuation of tests at 2 weeks 10. Inter- and intra-rater reliability by repeating of index tests by the same and by an alternative operator for the assessment at 2 weeks |
| Overall study start date | 01/09/2021 |
| Completion date | 14/02/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 600; UK Sample Size: 600 |
| Total final enrolment | 604 |
| Key inclusion criteria | Known history of diabetes |
| Key exclusion criteria | 1. Peripheral arterial disease (PAD) status known on imaging 2. Known history of PAD intervention 3. CTA and MRA contraindications; renal impairment, pregnancy, contrast medium hypersensitivity/allergy, non-compatible implants (MRA only) 4. Interim surgical interventions (occurring in the time interval between the index and reference tests) will be considered a protocol violation and patients will be excluded 5. Unable to provide appropriate informed consent |
| Date of first enrolment | 01/03/2022 |
| Date of final enrolment | 28/02/2023 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
London
W2 1BL
United Kingdom
London
SW10 9NH
United Kingdom
Leicester
LE1 5WW
United Kingdom
Southampton
SO16 6YD
United Kingdom
Hull
HU3 2JZ
United Kingdom
Derriford
Plymouth
PL6 8DH
United Kingdom
Worcester
WR5 1DD
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
5-7 Parsons Green
Fulham
SW6 4UL
United Kingdom
Westcliff-On-Sea
SS0 0RY
United Kingdom
London
SW17 0QT
United Kingdom
Cardiff
CF24 0SZ
United Kingdom
Glasgow
G51 4TF
United Kingdom
London
NW1 5JD
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
Derby
DE22 3NE
United Kingdom
Sponsor information
University/education
c/o Keith Boland
Joint Research Compliance Office
Room 221, Level 2, Medical School Building
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +44 (0)2075949480 |
|---|---|
| k.boland@imperial.ac.uk | |
| Website | http://www.imperial.ac.uk/ |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Government
No information available
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 28/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. Additional documents will be available once REC approval is in place. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
11/11/2024: The intention to publish date was changed from 27/11/2024 to 28/02/2025.
15/08/2024: The following changes were made to the study record:
1. The target number of participants was changed from 730 to 600.
2. St Cadoc's Hospital, King's College Hospital, Queen Alexandra Hospital, Musgrove Park Hospital, Gartnavel Royal Hospital, Solent NHS Trust Headquarters and Carmel Medical Practice were removed and St George's Hospital, Cardiff Royal Infirmary, Queen Elizabeth University Hospital, Hammersmith & Fulham Health and Care Partnership, Churchill Hospital and Royal Derby Hospital were added to the study participating centres.
13/08/2024: The following changes have been made:
1. The overall study end date was changed from 31/08/2024 to 14/02/2024.
2. The intention to publish date was changed from 01/08/2025 to 27/11/2024.
3. Total final enrolment added.
08/08/2023: The following changes have been made:
1. The overall study end date has been changed from 31/08/2023 to 31/08/2024 and the plain English summary updated accordingly.
2. The intention to publish date has been changed from 01/08/2024 to 01/08/2025.
07/03/2022: Ethics approval details and ClinicalTrials.gov number added.
15/10/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
