Endothelial Function Evaluation in Patients With PAOD Treated With Sulodexide + Conventional Treatment (CT) Vs CT Alone

Study Overview
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Brief Summary
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A randomized Multicentric open-label controlled trial. The primary objective of the study is to assess the improvement of endothelial function under sulodexide + conventional treatment or conventional treatment alone in patients with Leriche-Fontaine stage II peripheral arterial obstructive disease (systolic ankle brachial index ABI < 0. 9).

Detailed Description
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A randomized Multicentric open-label controlled trial. The primary objective of the study is to assess the improvement of endothelial function under sulodexide + conventional treatment (antiplatelet therapy; plus ACE inhibitor; plus Statin in patients with cholesterol total level > 1,35 g/l) or conventional treatment alone in patients with Leriche-Fontaine stage II peripheral arterial obstructive disease (systolic ankle brachial index ABI < 0. 9). Criteria for efficacy evaluation are the assessement of the improvement of the Digital Thermal monitoring between base line (day 1) and day 180 measured by Vendys® and the measurement of the correlation between the Digital Thermal monitoring and the following parameters at base line, day 90 and day 180: Von Willebrand factor blood level. Clinical assessment as per pain free walking distance and maximum walking distance, as measured by walking machine. Fibrinogen blood level. Also an assessment of the study medication observance (patient's compliance) will be done. Safety assessment will be done through the collection of the adverse events occurred during the study.

Official Title
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A Multicentric Open-label Randomized Controlled Study for Evaluating the Improvement of Endothelial Function in Stage II Peripheral Arterial Obstructive Disease Patients Treated With Sulodexide + Conventional Treatment {CT] Vs CT Alone

Conditions
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Peripheral Arterial Obstructive Disease

Intervention / Treatment
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* Drug: Sulodexide
* Drug: Statin
* Drug: Antiplatelet Agents
* Drug: ACE inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intermittent claudication. A systolic ankle brachial index ABI < 0. 9 An age of over 40 years At least one cardiovascular risk factor (active or weaned Smoking, diabetes mellitus, hypertension, lipid disorders, obesity, and erectile dysfunction) or a history of coronary artery disease or transient ischemic stroke or established. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study Exclusion Criteria: withdrawal of informed consent participation in another clinical trial with investigational drugs within the last 12 weeks or during the present trial period history of hypersensitivity to the investigational/conventional drugs Non claudicating patients and patients with critical ischemia Arteritis of non-atherosclerotic origin Patients treated with the oxalate or Naftidrofuryl Pentoxifiline Cilostazol or within 3 months that preceded the inclusion Patients receiving other agents that alter the secretion of NO (such as Sildenafil and Tadalafil) less than 2 weeks before inclusion Patients receiving a regimen based on nitrates or molsidomine or Bosentan Patients receiving Anti Vitamin K medication (AVK) Hemorrhagic accident dating less than 15 days before inclusion Heparin treatment or any treatment by low molecular weight heparins during the study for a continuous period of more than 10 days or a cumulative time during the study for more than 21 days.

Ages Eligible for Study
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Minimum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Multicentric open-label controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CT group<br>78 patients will be treated by conventional treatment : antiplatelet therapy + ACE inhibitor +/- Statin in patients with cholesterol total level > 1,35 g/l | Drug: Statin<br>* Statin 20mg once daily per oral route,<br>* Other names: Atorvastatin or equivalent;Drug: Antiplatelet Agents<br>* Antiplatelet therapy 75mg once daily per oral route<br>* Other names: lysine acetylsalicylate or equivalent;Drug: ACE inhibitor<br>* ACE inhibitor 20mg once daily per oral route<br>* Other names: Captopril or equivalent;|
| Experimental: Sulodexide + CT group<br>78 patients will be treated by : Sulodexide (250ULS, twice daily , oral administration) Conventional treatment : antiplatelet agents + ACE inhibitor +/- Statin in patients with cholesterol total level > 1,35 g/l | Drug: Sulodexide<br>* Sulodexide 250 ULS twice daily per oral route<br>* Other names: Vessel;Drug: Statin<br>* Statin 20mg once daily per oral route,<br>* Other names: Atorvastatin or equivalent;Drug: Antiplatelet Agents<br>* Antiplatelet therapy 75mg once daily per oral route<br>* Other names: lysine acetylsalicylate or equivalent;Drug: ACE inhibitor<br>* ACE inhibitor 20mg once daily per oral route<br>* Other names: Captopril or equivalent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline endothelial function after 6 months | Assess the improvement of the Digital Thermal monitoring measured by Vendys®: evaluation of the improvement of Fingertip Digital Thermal Monitoring (DTM) and the detection of a significant change of the FT2 parameters as per Endothelix discriminative values provided by the manufacturer between day 1 and day 180 (±15 days). | between base line (day 1) and day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metric change of the walking distance | Metric variation of the walking distance: Clinical assessment as per pain free walking distance and maximum walking distance, measured by walking machine. A significant change for more than 30% of the walking distance at the assessment point, to consider it an improvement while analysing. | base line, day 90 and day 180: | 
| Change in Von Willebrand Factor (VWF) level | Evidence of significant change in VWF level: Serum levels of Von Willebrand Factor will be measured by immunoturbidiometric method. An improvement of the level of VWF blood level by at least 10% in 1st assessment and 30% in last assessment compared to baseline values | base line, day 90 and day 180 | 
| Assessment of the study medication observance patient's compliance | Compliance will be stated in accordance to the results stated by the patients during remote monitoring at days, 30, 80, 170, and the drug accountability performed by doctors at days 90 and 180. It will be measured in % of the total destined dose expressed in number of intakes and days of treatment. | 180 days | 
| Assessment of safety | Safety will be assessed by checklist questioning during visits and remote interactions, investigators will be responsible for collection and notification to the Sponsor and authorities in case of Serious Adverse Events. | 180 days |