Peripheral Microvascular Resistance as a Predictor for Limb Salvage

Study Overview
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Brief Summary
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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.

Official Title
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Peripheral Microvascular Resistance as a Predictor for Limb Salvage in Post-Intervention Critical Limb Ischemia Patients

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Diagnostic Test: Peripheral vascular flow reserve measurement


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peripheral vascular flow reserve measurement<br>Post-procedure peripheral vascular flow reserve by thermodilution will be measured by the pressure wire. | Diagnostic Test: Peripheral vascular flow reserve measurement<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the peripheral flow reserve | 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. | 6 months post-endovascular intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom resolution - Ulcer healing (1m) | Ulcer healing: changes in the number and extent of leg ulcers compared to baseline. | 1 month post-endovascular intervention | 
| Symptom resolution - Ulcer healing (6m) | Ulcer healing: changes in the number and extent of leg ulcers compared to baseline. | 6 months post-endovascular intervention | 
| Number of patients with Symptom resolution - Pain (1m) | Resolution of rest pain and alteration in visual analogue pain compared to baseline. | 1 month post-endovascular intervention | 
| Number of patients with Symptom resolution - Pain (6m) | Resolution of rest pain and alteration in visual analogue pain compared to baseline. | 6 months post-endovascular intervention | 
| Ankle-brachial index (ABI) (1m) | 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. | 1 month post-endovascular intervention | 
| Ankle-brachial index (ABI) (6m) | 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. | 6 months post-endovascular intervention | 
| Toe-brachial index (TBI) (1m) | 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. | 1 month post-endovascular intervention | 
| Toe-brachial index (TBI) (6m) | 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. | 6 months post-endovascular intervention | 
| Rutherford classification (1m) | 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. | 1 month post-endovascular intervention | 
| Rutherford classification (6m) | 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. | 6 months post-endovascular intervention | 
| Transcutaneous oxygen partial pressure (TcPO2) (1m) | 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). | 1 month post-endovascular intervention | 
| Transcutaneous oxygen partial pressure (TcPO2) (6m) | 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). | 6 months post-endovascular intervention | 
| Target lesion revascularization (1m) | Need for revascularization (yes/no) | At 1 month post-endovascular intervention | 
| Target lesion revascularization (6m) | Need for revascularization (yes/no) | At 6 month post-endovascular intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microvascular disease, Microvascular Resistance, Limb Salvage, Peripheral Arterial Disease, critical limb ischemia