Efficacy and Safety of the Regulatory Polypeptides in Patients With Peripheral Atherosclerosis.

Study Overview
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Brief Summary
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The study is aimed at assessing the role of the activity of markers of endothelial dysfunction (cytotoxic malonic aldehyde (MDA), angiotensin II, endothelial nitric oxide synthase (NO), endothelin-1, prostacyclin) in the systemic circulation in patients with lower extremity atherosclerotic arterial occlusive disease undergoing open reconstructive interventions.

Detailed Description
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The study will include 120 patients of similar age, gender, and ethnicity, they will be divided into four groups: Group I: 30 patients with lower extremity atherosclerotic arterial occlusive disease, stage IIA-IIB of the disease according to the Fontaine-Pokrovsky classification, receiving conservative therapy; Group II: 30 patients with lower extremity atherosclerotic arterial occlusive disease, stage IIA-IIB of the disease according to the Fontaine-Pokrovsky classification, receiving conservative therapy, including the drug based on vascular polypeptides Slavinorm®; Group III: 30 patients with lower extremity atherosclerotic arterial occlusive disease, stageIII-IV of the disease according to the Fontaine-Pokrovsky classification, receiving conservative therapy in combination with surgical methods of treatment (femoral-popliteal bypass grafting with a synthetic graft above the knee); Group IV: 30 patients with lower extremity atherosclerotic arterial occlusive disease, stage III-IV of the disease according to the Fontaine-Pokrovsky classification, receiving conservative therapy, including the drug based on vascular polypeptides Slavinorm®, in combination with surgical methods of treatment (femoral-popliteal bypass grafting with a synthetic graft above the knee).

Official Title
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Evaluation of the Efficacy and Safety of the Drug Based on Vascular Regulatory Polypeptides for the Treatment of Patients With Lower Extremity Atherosclerotic Arterial Occlusive Disease.

Conditions
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Peripheral Arterial Occlusive Disease

Intervention / Treatment
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* Drug: Polypeptides
* Device: Femoral-popliteal bypass grafting with a synthetic graft above the knee
* Other: Routine conservative treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men or women over 18 years of age with lower extremity atherosclerotic arterial occlusive disease, confirmed with instrumental work-up methods (ultrasonography or angiography). Exclusion Criteria: men or women under 18 years of age; history of anaphylaxis; hypersensitivity to any of the components that make up the drug Slavinorm®, and proteins of animal origin; absolute and relative contraindications to the treadmill test; failure to walk at a minimum speed of 3.2 km/h (2 mph) at a minimum treadmill angle for at least 2 minutes during the stress test during the screening phase; depression of the ST segment more than 1 mm in one or more standard leads on the electrocardiogram; peripheral artery disease not associated with atherosclerosis; patients who underwent reconstructive surgery or invasive interventions on the arteries of the lower extremities in history without a clinic of intermittent claudication; angina pectoris III-IV functional class (FC) according to the CCS classification; body mass index >35 kg/m2; acute or chronic renal (creatinine clearance less than 30 ml / min) and / or liver failure [aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 3 times the upper limit of normal]; chronic heart failure III-IV FC according to NYHA; acute coronary syndrome within 6 months. before the start of the screening period; any clinically significant condition or comorbidity that, in the opinion of the Investigator, would preclude the patient from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open, prospective study is aimed at enrolling 120 patients with lower extremity atherosclerotic arterial occlusive disease. Patients are planned to undergo conservative therapy according to indications, including the use of a drug based on vascular polypeptides Slavinorm®, as well as a combination of conservative therapy, including a drug based on vascular polypeptides Slavinorm®, with surgical methods of treatment (femoral-popliteal bypass grafting with a synthetic graft above the knee). Subjects of similar age, gender, and ethnicity should be divided into four groups, respectively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients who undergo routine conservative treatment<br>The patients who undergo routine conservative treatment for peripheral atherosclerotic occlusive disease as per clinical guidelines | Other: Routine conservative treatment<br>* The patients will undergo routine conservative treatment as per clinical guidelines (acetylsalicylic acid 100mg daily, atorvastatin 20mg daily)<br>|
| Experimental: Patients who undergo treatment with polypeptides<br>The patients who undergo treatment with a complex of polypeptides isolated from the vessels of cattle is administered in / m, adults 1 vial (5 mg) 1 time / day 2 times a week. The course of treatment is 10 injections. | Drug: Polypeptides<br>* The patients will undergo treatment with a drug based on vascular polypeptides Slavinorm®, a derivative from cattle vessels, registered in Russia for the treatment of patients with peripheral atherosclerotic occlusive disease.<br>* Other names: vascular polypeptides Slavinorm®, a derivative from cattle vessels;|
| Active Comparator: Patients who undergo femoral-popliteal bypass with a synthetic graft above the knee<br>Patients who undergo the surgical method of treatment i.e. femoral-popliteal bypass grafting with a synthetic graft above the knee and routine conservative treatment as per clinical guidelines | Device: Femoral-popliteal bypass grafting with a synthetic graft above the knee<br>* The patients with undergo an arterial revascularization - Femoral-popliteal bypass grafting with a synthetic graft above the knee<br>Other: Routine conservative treatment<br>* The patients will undergo routine conservative treatment as per clinical guidelines (acetylsalicylic acid 100mg daily, atorvastatin 20mg daily)<br>|
| Experimental: Patients who undergo femoral-popliteal bypass grafting and treatment with polypeptides<br>Patients who undergo the surgical method of treatment i.e. femoral-popliteal bypass grafting with a synthetic graft above the knee with following treatment with a complex of polypeptides isolated from the vessels of cattle is administered in / m, adults 1 vial (5 mg) 1 time / day 2 times a week. The course of treatment is 10 injections. | Drug: Polypeptides<br>* The patients will undergo treatment with a drug based on vascular polypeptides Slavinorm®, a derivative from cattle vessels, registered in Russia for the treatment of patients with peripheral atherosclerotic occlusive disease.<br>* Other names: vascular polypeptides Slavinorm®, a derivative from cattle vessels;Device: Femoral-popliteal bypass grafting with a synthetic graft above the knee<br>* The patients with undergo an arterial revascularization - Femoral-popliteal bypass grafting with a synthetic graft above the knee<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower artery or bypass graft thrombosis | The rate of the Lower artery or bypass graft thrombosis | 1 year | 
| disease progression | The rate of the disease progression | 1 year | 
| restenosis | Restenosis rate | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| limb loss | Limb loss rate | 1 year | 
| changes in pain-free walking distance | Changes in the parameter of pain-free walking distance (in meters) | 1 year | 
| changes in ankle-brachial index | Changes in the parameter of ankle-brachial index measured at rest | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Arterial Disease, bypass grafting, polypeptides