Critical Limb Ischemia, Critical Lower Limb Ischemia, Diabetic Foot, Diabetic Foot Ulcer, Peripheral Arterial Disease, Peripheral Artery Disease, Peripheral Vascular Diseases
Conditions
Brief summary
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 (known as peripheral arterial disease (PAD)). However, there is confusion as to which is the gold standard. The DM PAD study aims 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 PAD in patients with diabetes as determined by a reference test (CTA or MRA).
Interventions
DIAGNOSTIC_TESTToe Brachial Pressure Index (TBPI)
TBPI will be measured using the photoplethysmography (PPG) method, employing an infrared sensor placed on the hallux and index finger.
DIAGNOSTIC_TESTAnkle Brachial Pressure Index (ABPI)
A sphygmomanometer-cuff placed at the ankle and a handheld continuous wave Doppler device will be used to measure the systolic pressure of the dorsalis pedis and posterior tibial artery.
DIAGNOSTIC_TESTExercise Ankle Brachial Pressure Index (ABPI)
A sphygmomanometer-cuff placed at the ankle and a handheld continuous wave Doppler device will be used to measure the systolic pressure of the dorsalis pedis and posterior tibial artery, following the participant completing 50 consecutive repetitions of active dorsiflexion whilst standing.
DIAGNOSTIC_TESTAudible handheld Doppler
Audible CW Doppler interrogation of the dorsalis pedis and posterior tibial artery.
DIAGNOSTIC_TESTVisual handheld Doppler
Visual CW interrogation of the dorsalis pedis and posterior tibial artery was performed using the handheld Huntleigh Digital Dopplex device.
DIAGNOSTIC_TESTPodiatry Ankle Duplex scan (PAD-scan)
Podiatry ankle duplex scan (PAD-scan) involves using an ultrasound machine to visualise the anterior and posterior tibial arteries at the ankle. To be used in 3 participating centers only.
Sponsors
University of Leicester
University of Edinburgh
Universidad de Granada
Imperial College London
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 years * Known history of diabetes
Exclusion criteria
* PAD status known on imaging * Known history of PAD intervention * CTA and MRA contraindications- renal impairment, pregnancy, contrast medium hypersensitivity/allergy, non-compatible implants (MRA only). * Unable to provide appropriate informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Accuracy | 6 weeks; all index tests will be performed on the same day of presentation; reference scan performed within six weeks of the index tests. | Diagnostic accuracy of the PAD-scan and other bedside tests will be compared to the results of a Magnetic resonance angiograph (MRA) or Computed tomography angiography (CTA) (reference test). |
| Diagnostic Accuracy - Ratios | 6 weeks; all index tests will be performed on the same day of presentation; reference scan performed within six weeks of the index tests. | Diagnostic accuracy of the PAD-scan and other bedside tests will be compared to the results of a Magnetic resonance angiograph (MRA) or Computed tomography angiography (CTA) (reference test). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health Economic Outcome - Cost Effectiveness | 5 years | Incremental cost-effectiveness ratio at 5 years. |
| Health Economic Outcome - Cost Effectiveness (QALY) | 5 years | Incremental cost-effectiveness ratio at 5 years. |
| Patient Acceptability | 1 hour: all index tests will be performed on the same day of presentation. | Patients will be asked to rate their experience of each index test on a Likert scale. |
| Technical Success | 6 weeks; all index tests will be performed on the same day of presentation; reference scan performed within six weeks of the index tests. | Inability to perform, refusal and discontinuation of tests will be documented |
Countries
United Kingdom
Participant flow
Pre-assignment details
Patients are assessed for eligibility and some are excluded as per eligibility criteria
Participants by arm
| Arm | Count |
|---|---|
| All Participants Diagnostic Test: Toe Brachial Pressure Index (TBPI) TBPI will be measured using the photoplethysmography (PPG) method, employing an infrared sensor placed on the hallux and index finger.
Diagnostic Test: Ankle Brachial Pressure Index (ABPI) A sphygmomanometer-cuff placed at the ankle and a handheld continuous wave Doppler device will be used to measure the systolic pressure of the dorsalis pedis and posterior tibial artery.
Diagnostic Test: Exercise Ankle Brachial Pressure Index (ABPI) A sphygmomanometer-cuff placed at the ankle and a handheld continuous wave Doppler device will be used to measure the systolic pressure of the dorsalis pedis and posterior tibial artery, following the participant completing 50 consecutive repetitions of active dorsiflexion whilst standing.
Diagnostic Test: Audible handheld Doppler Audible CW Doppler interrogation of the dorsalis pedis and posterior tibial artery.
Diagnostic Test: Visual handheld Doppler Visual CW interrogation of the dorsalis pedis and posterior tibial artery was performed using the handheld Huntleigh Digital Dopplex device.
Diagnostic Test: Podiatry Ankle Duplex scan (PAD-scan) Podiatry ankle duplex scan (PAD-scan) involves using an ultrasound machine to visualise the anterior and posterior tibial arteries at the ankle.
To be used in 3 participating centers only. | 603 |
| Total | 603 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 61.48 years STANDARD_DEVIATION 12.78 |
| Diabetes mellitus type Missing | 8 Participants |
| Diabetes mellitus type Type 1 | 115 Participants |
| Diabetes mellitus type Type 2 | 480 Participants |
| Foot examination - Infection No | 576 Participants |
| Foot examination - Infection Yes | 27 Participants |
| Foot examination - Neuropathy present in index limb No | 455 Participants |
| Foot examination - Neuropathy present in index limb Yes | 148 Participants |
| Foot examination - ulceration No | 521 Participants |
| Foot examination - ulceration Yes | 82 Participants |
| Gangrene No | 595 Participants |
| Gangrene Yes | 8 Participants |
| Leg pain at rest No | 438 Participants |
| Leg pain at rest Yes | 165 Participants |
| Leg pain whilst exercising No | 446 Participants |
| Leg pain whilst exercising Yes | 157 Participants |
| Overall WIfI Score High | 3 Participants |
| Overall WIfI Score Low | 13 Participants |
| Overall WIfI Score Missing | 7 Participants |
| Overall WIfI Score Moderate | 16 Participants |
| Overall WIfI Score Very Low | 564 Participants |
| Previous history of diabetic foot ulcer No | 595 Participants |
| Previous history of diabetic foot ulcer Yes | 68 Participants |
| Race/Ethnicity, Customized Asian | 83 Participants |
| Race/Ethnicity, Customized Black | 47 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized Mixed race / multiple ethnic background | 12 Participants |
| Race/Ethnicity, Customized Other ethnic group | 31 Participants |
| Race/Ethnicity, Customized White | 429 Participants |
| Sex: Female, Male Female | 215 Participants |
| Sex: Female, Male Male | 388 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 604 |
| other Total, other adverse events | 4 / 604 |
| serious Total, serious adverse events | 0 / 604 |
Outcome results
Primary
Diagnostic Accuracy
Diagnostic accuracy of the PAD-scan and other bedside tests will be compared to the results of a Magnetic resonance angiograph (MRA) or Computed tomography angiography (CTA) (reference test).
Time frame: 6 weeks; all index tests will be performed on the same day of presentation; reference scan performed within six weeks of the index tests.
Population: Number of participants who underwent the index test
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Audible Doppler | Diagnostic Accuracy | Positive Predictive Value (PPV) | 75 percentage |
| Audible Doppler | Diagnostic Accuracy | Specificity | 93 percentage |
| Audible Doppler | Diagnostic Accuracy | Negative Predictive Value (NPV) | 72 percentage |
| Audible Doppler | Diagnostic Accuracy | Sensitivity | 36 percentage |
| Visual Doppler | Diagnostic Accuracy | Positive Predictive Value (PPV) | 63 percentage |
| Visual Doppler | Diagnostic Accuracy | Specificity | 86 percentage |
| Visual Doppler | Diagnostic Accuracy | Sensitivity | 42 percentage |
| Visual Doppler | Diagnostic Accuracy | Negative Predictive Value (NPV) | 72 percentage |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy | Specificity | 78 percentage |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy | Positive Predictive Value (PPV) | 58 percentage |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy | Sensitivity | 55 percentage |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy | Negative Predictive Value (NPV) | 76 percentage |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Sensitivity | 41 percentage |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Positive Predictive Value (PPV) | 59 percentage |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Specificity | 84 percentage |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Negative Predictive Value (NPV) | 71 percentage |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Sensitivity | 41 percentage |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Specificity | 83 percentage |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Positive Predictive Value (PPV) | 55 percentage |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy | Negative Predictive Value (NPV) | 74 percentage |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy | Negative Predictive Value (NPV) | 93 percentage |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy | Specificity | 69 percentage |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy | Sensitivity | 89 percentage |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy | Positive Predictive Value (PPV) | 57 percentage |
Primary
Diagnostic Accuracy - Ratios
Diagnostic accuracy of the PAD-scan and other bedside tests will be compared to the results of a Magnetic resonance angiograph (MRA) or Computed tomography angiography (CTA) (reference test).
Time frame: 6 weeks; all index tests will be performed on the same day of presentation; reference scan performed within six weeks of the index tests.
Population: Number of participants who underwent the index test
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Audible Doppler | Diagnostic Accuracy - Ratios | Positive Likelihood Ratio (PLR) | 5.3 ratio |
| Audible Doppler | Diagnostic Accuracy - Ratios | Negative Likelihood Ratio (NLR) | 0.7 ratio |
| Audible Doppler | Diagnostic Accuracy - Ratios | Odds Ratio (OR) | 7.7 ratio |
| Visual Doppler | Diagnostic Accuracy - Ratios | Positive Likelihood Ratio (PLR) | 3.0 ratio |
| Visual Doppler | Diagnostic Accuracy - Ratios | Negative Likelihood Ratio (NLR) | 0.7 ratio |
| Visual Doppler | Diagnostic Accuracy - Ratios | Odds Ratio (OR) | 4.4 ratio |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy - Ratios | Positive Likelihood Ratio (PLR) | 2.5 ratio |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy - Ratios | Negative Likelihood Ratio (NLR) | 0.6 ratio |
| Toe Brachial Pressure Index (TBPI) | Diagnostic Accuracy - Ratios | Odds Ratio (OR) | 4.2 ratio |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy - Ratios | Positive Likelihood Ratio (PLR) | 2.6 ratio |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy - Ratios | Negative Likelihood Ratio (NLR) | 0.7 ratio |
| Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy - Ratios | Odds Ratio (OR) | 3.7 ratio |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy - Ratios | Positive Likelihood Ratio (PLR) | 2.4 ratio |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy - Ratios | Negative Likelihood Ratio (NLR) | 0.7 ratio |
| Exercise Ankle Brachial Pressure Index (ABPI) | Diagnostic Accuracy - Ratios | Odds Ratio (OR) | 3.4 ratio |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy - Ratios | Negative Likelihood Ratio (NLR) | 0.2 ratio |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy - Ratios | Odds Ratio (OR) | 18.8 ratio |
| Podiatry Ankle Duplex Scan (PAD-scan) | Diagnostic Accuracy - Ratios | Positive Likelihood Ratio (PLR) | 2.9 ratio |
Secondary
Health Economic Outcome - Cost Effectiveness
Incremental cost-effectiveness ratio at 5 years.
Time frame: 5 years
Population: The costs over 5 years for a hypothetical cohort of 1000 diabetic patients that is similar to the DM PAD cohort.~Weighted average costs.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Audible Doppler | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11165437 GBP |
| Audible Doppler | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 37186446 GBP |
| Visual Doppler | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11204467 GBP |
| Visual Doppler | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 37310327 GBP |
| Toe Brachial Pressure Index (TBPI) | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11241003 GBP |
| Toe Brachial Pressure Index (TBPI) | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 37607662 GBP |
| Ankle Brachial Pressure Index (ABPI) | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11218496 GBP |
| Ankle Brachial Pressure Index (ABPI) | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 37273035 GBP |
| Exercise Ankle Brachial Pressure Index (ABPI) | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11229209 GBP |
| Exercise Ankle Brachial Pressure Index (ABPI) | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 37267357 GBP |
| Podiatry Ankle Duplex Scan (PAD-scan) | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11156745 GBP |
| Podiatry Ankle Duplex Scan (PAD-scan) | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 36240553 GBP |
| DUS for All | Health Economic Outcome - Cost Effectiveness | Cost (£) | 11413487 GBP |
| DUS for All | Health Economic Outcome - Cost Effectiveness | Net benefit (£) | 38641671 GBP |
Secondary
Health Economic Outcome - Cost Effectiveness (QALY)
Incremental cost-effectiveness ratio at 5 years.
Time frame: 5 years
Population: Hypothetical cohort of 1000 diabetic patients that is similar to the DM PAD cohort
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Audible Doppler | Health Economic Outcome - Cost Effectiveness (QALY) | 2418 Quality Adjusted Life Years |
| Visual Doppler | Health Economic Outcome - Cost Effectiveness (QALY) | 2426 Quality Adjusted Life Years |
| Toe Brachial Pressure Index (TBPI) | Health Economic Outcome - Cost Effectiveness (QALY) | 2442 Quality Adjusted Life Years |
| Ankle Brachial Pressure Index (ABPI) | Health Economic Outcome - Cost Effectiveness (QALY) | 2425 Quality Adjusted Life Years |
| Exercise Ankle Brachial Pressure Index (ABPI) | Health Economic Outcome - Cost Effectiveness (QALY) | 2425 Quality Adjusted Life Years |
| Podiatry Ankle Duplex Scan (PAD-scan) | Health Economic Outcome - Cost Effectiveness (QALY) | 2370 Quality Adjusted Life Years |
| DUS for All | Health Economic Outcome - Cost Effectiveness (QALY) | 2503 Quality Adjusted Life Years |
Secondary
Patient Acceptability
Patients will be asked to rate their experience of each index test on a Likert scale.
Time frame: 1 hour: all index tests will be performed on the same day of presentation.
Population: Participant that underwent the index test
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Audible Doppler | Patient Acceptability | Missing | 4 participants |
| Audible Doppler | Patient Acceptability | Neutral | 6 participants |
| Audible Doppler | Patient Acceptability | Very satisfied | 501 participants |
| Audible Doppler | Patient Acceptability | Satisfied | 84 participants |
| Audible Doppler | Patient Acceptability | Very unsatisfied | 7 participants |
| Audible Doppler | Patient Acceptability | Unsatisfied | 1 participants |
| Visual Doppler | Patient Acceptability | Satisfied | 81 participants |
| Visual Doppler | Patient Acceptability | Very unsatisfied | 7 participants |
| Visual Doppler | Patient Acceptability | Neutral | 5 participants |
| Visual Doppler | Patient Acceptability | Very satisfied | 503 participants |
| Visual Doppler | Patient Acceptability | Unsatisfied | 1 participants |
| Visual Doppler | Patient Acceptability | Missing | 6 participants |
| Toe Brachial Pressure Index (TBPI) | Patient Acceptability | Neutral | 6 participants |
| Toe Brachial Pressure Index (TBPI) | Patient Acceptability | Missing | 15 participants |
| Toe Brachial Pressure Index (TBPI) | Patient Acceptability | Unsatisfied | 0 participants |
| Toe Brachial Pressure Index (TBPI) | Patient Acceptability | Very unsatisfied | 7 participants |
| Toe Brachial Pressure Index (TBPI) | Patient Acceptability | Satisfied | 81 participants |
| Toe Brachial Pressure Index (TBPI) | Patient Acceptability | Very satisfied | 494 participants |
| Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Satisfied | 89 participants |
| Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Missing | 9 participants |
| Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Unsatisfied | 6 participants |
| Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Very unsatisfied | 11 participants |
| Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Neutral | 13 participants |
| Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Very satisfied | 475 participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Neutral | 12 participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Very satisfied | 435 participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Satisfied | 77 participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Missing | 65 participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Very unsatisfied | 8 participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Patient Acceptability | Unsatisfied | 6 participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Patient Acceptability | Missing | 0 participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Patient Acceptability | Very unsatisfied | 2 participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Patient Acceptability | Unsatisfied | 0 participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Patient Acceptability | Neutral | 2 participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Patient Acceptability | Satisfied | 21 participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Patient Acceptability | Very satisfied | 77 participants |
Secondary
Technical Success
Inability to perform, refusal and discontinuation of tests will be documented
Time frame: 6 weeks; all index tests will be performed on the same day of presentation; reference scan performed within six weeks of the index tests.
Population: Recruited participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Audible Doppler | Technical Success | Assessment performed - no | 0 Participants |
| Audible Doppler | Technical Success | Assessment performed - yes | 603 Participants |
| Audible Doppler | Technical Success | Assessment discontinued - yes | 0 Participants |
| Audible Doppler | Technical Success | Assessment discontinued - no | 603 Participants |
| Visual Doppler | Technical Success | Assessment performed - yes | 603 Participants |
| Visual Doppler | Technical Success | Assessment discontinued - yes | 0 Participants |
| Visual Doppler | Technical Success | Assessment performed - no | 0 Participants |
| Visual Doppler | Technical Success | Assessment discontinued - no | 603 Participants |
| Toe Brachial Pressure Index (TBPI) | Technical Success | Assessment discontinued - yes | 4 Participants |
| Toe Brachial Pressure Index (TBPI) | Technical Success | Assessment performed - yes | 590 Participants |
| Toe Brachial Pressure Index (TBPI) | Technical Success | Assessment discontinued - no | 586 Participants |
| Toe Brachial Pressure Index (TBPI) | Technical Success | Assessment performed - no | 13 Participants |
| Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment performed - yes | 599 Participants |
| Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment performed - no | 4 Participants |
| Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment discontinued - yes | 3 Participants |
| Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment discontinued - no | 596 Participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment performed - yes | 540 Participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment performed - no | 63 Participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment discontinued - no | 533 Participants |
| Exercise Ankle Brachial Pressure Index (ABPI) | Technical Success | Assessment discontinued - yes | 7 Participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Technical Success | Assessment performed - no | 1 Participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Technical Success | Assessment performed - yes | 102 Participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Technical Success | Assessment discontinued - yes | 0 Participants |
| Podiatry Ankle Duplex Scan (PAD-scan) | Technical Success | Assessment discontinued - no | 102 Participants |