Peripheral Arterial Disease
Conditions
Keywords
Microvascular disease, Microvascular Resistance, Limb Salvage, Peripheral Arterial Disease, critical limb ischemia
Brief summary
Salvaging a threatened limb is the key therapeutic objective for patients with critical limb ischemia, and the achievement of limb salvage is an independent predictor of patient morbidity and mortality. Despite successful primary endovascular or surgical intervention, the corresponding symptoms of rest pain and/or non-healing ulceration in some patients may continue, and amputation in these patients is unavoidable. It is hypothesized that the functional integrity of the peripheral vascular microcirculation may be impaired in these patients. However, there are currently no techniques that allow direct quantification and visualization of the microcirculation due to the micro-vessel invisibility under angiography. In the coronary circulation, coronary flow reserve (CFR) indicates the capacity for maximal hyperemic blood flow and reveals impaired coronary microvascular function. Studies have shown the clinical significance of measuring microvascular resistance to predict myocardial salvage after myocardial infarction. The study will explore whether this concept of coronary flow reserve can be applied peripherally to patients with critical limb ischemia in order to determine whether measuring peripheral vascular flow reserve can determine the integrity of the microcirculation to predict limb salvage after endovascular intervention.
Interventions
DIAGNOSTIC_TESTPeripheral vascular flow reserve measurement
Peripheral arterial (below knee popliteal and above the level of ankle distal tibial) thermodilution curves will be obtained. One of the distal tibial arteries (anterior tibial, posterior tibial or peroneal artery, whichever reaches the most distal part of the foot in the run off) will be picked for measurements. At room temperature, 3 ml of saline will be injected brisk manually to determine the peak arterial flow, presented as mean transit time (Tmn). Resting Tmn will be performed and averaged by triplicate measurements at baseline. Then maximal hyperemia will be induced by intra-arterial injection of 30 mg papaverine through the guiding catheter, then 3 ml of saline will be injected to get hyperemic Tmn averaged by triplicate measurements. The guidewire will be kept in a fixed position during the series of measurements. Peripheral vascular flow reserve was calculated as resting Tmn divided by hyperemic Tmn (Fukunaga 2015).
Sponsors
Abbott Medical Devices
Hackensack Meridian Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic critical limb ischemia (Rutherford 4-6). * Age ≥18 years * Ability and willingness to sign the IRB approved Informed Consent form
Exclusion criteria
* Non-reconstructable chronic total occlusive disease of the proximal inflow vessels that would make flow reserve measurements impossible. * Non-salvageable lower extremity due to infection or overwhelming per-existing tissue loss (most critical Rutherford 6 patients). * Inability to understand the study or a history of non-compliance with medical advice; * History of any cognitive or mental health status that would interfere with study participation; * Currently enrolled in any pre-approval investigational study. * Female subjects who are pregnant or nursing or planning to become pregnant within the study period; * Known sensitivity to contrast media, which can't be adequately pre-medicated; * Expected life span less than 6 months. * Unable to read/understand/sign the English Language consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of the peripheral flow reserve | 6 months post-endovascular intervention | To assess whether peripheral flow reserve can predict the success rate of limb salvage in critical limb ischemia patients after endovascular intervention. Assessed by any amputation (major or minor) at 6 months post-endovascular intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom resolution - Ulcer healing (6m) | 6 months post-endovascular intervention | Ulcer healing: changes in the number and extent of leg ulcers compared to baseline. |
| Number of patients with Symptom resolution - Pain (1m) | 1 month post-endovascular intervention | Resolution of rest pain and alteration in visual analogue pain compared to baseline. |
| Number of patients with Symptom resolution - Pain (6m) | 6 months post-endovascular intervention | Resolution of rest pain and alteration in visual analogue pain compared to baseline. |
| Ankle-brachial index (ABI) (1m) | 1 month post-endovascular intervention | Improvement in Ankle-brachial index (ABI) compared to baseline. The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. Normal ABI ranges from 1.0 - 1.4, with \<0.9 suggesting arterial disease. |
| Ankle-brachial index (ABI) (6m) | 6 months post-endovascular intervention | Improvement in Ankle-brachial index (ABI) compared to baseline. The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. Normal ABI ranges from 1.0 - 1.4, with \<0.9 suggesting arterial disease. |
| Toe-brachial index (TBI) (1m) | 1 month post-endovascular intervention | Improvement in Toe-brachial index (TBI) compared to baseline. The Toe Brachial Index (TBI) is defined as the ratio between the systolic blood pressure in the right or left toe and the higher of the systolic pressure in the right or left arms. TBI ≥ 0.7 is considered normal while TBI \< 0.7 is considered abnormal. |
| Symptom resolution - Ulcer healing (1m) | 1 month post-endovascular intervention | Ulcer healing: changes in the number and extent of leg ulcers compared to baseline. |
| Rutherford classification (1m) | 1 month post-endovascular intervention | Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene. |
| Rutherford classification (6m) | 6 months post-endovascular intervention | Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene. |
| Transcutaneous oxygen partial pressure (TcPO2) (1m) | 1 month post-endovascular intervention | Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion). |
| Transcutaneous oxygen partial pressure (TcPO2) (6m) | 6 months post-endovascular intervention | Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion). |
| Target lesion revascularization (1m) | At 1 month post-endovascular intervention | Need for revascularization (yes/no) |
| Target lesion revascularization (6m) | At 6 month post-endovascular intervention | Need for revascularization (yes/no) |
| Toe-brachial index (TBI) (6m) | 6 months post-endovascular intervention | Improvement in Toe-brachial index (TBI) compared to baseline. The Toe Brachial Index (TBI) is defined as the ratio between the systolic blood pressure in the right or left toe and the higher of the systolic pressure in the right or left arms. TBI ≥ 0.7 is considered normal while TBI \< 0.7 is considered abnormal. |
Outcome results
None listed