Endothelial Function Evaluation in Patients With PAOD Treated With Sulodexide + Conventional Treatment (CT) Vs CT Alone (AWAOMI2)

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

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).

Study Overview

• Status: Unknown
• Conditions: Peripheral Arterial Obstructive Disease
• Intervention / Treatment: Drug: Statin; Drug: Antiplatelet Agents; Drug: ACE inhibitor; Drug: Sulodexide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 3

Contacts and Locations

Study Locations

• Tunisia
  • Sfax, Tunisia, 3000
    • InvSite Poseidon0031
  • Sousse, Tunisia, 4000
    • InvSite Poseidon 0022
  • Tunis, Tunisia, 1006
    • InvSite Poseidon0011

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CT group; 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; Statin 20mg once daily per oral route,; Other Names: Atorvastatin or equivalent; Drug: Antiplatelet Agents; Antiplatelet therapy 75mg once daily per oral route; Other Names: lysine acetylsalicylate or equivalent; Drug: ACE inhibitor; ACE inhibitor 20mg once daily per oral route; Other Names: Captopril or equivalent
Experimental: Sulodexide + CT group; 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: Statin; Statin 20mg once daily per oral route,; Other Names: Atorvastatin or equivalent; Drug: Antiplatelet Agents; Antiplatelet therapy 75mg once daily per oral route; Other Names: lysine acetylsalicylate or equivalent; Drug: ACE inhibitor; ACE inhibitor 20mg once daily per oral route; Other Names: Captopril or equivalent; Drug: Sulodexide; Sulodexide 250 ULS twice daily per oral route; Other Names: Vessel

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alfa Wassermann Tunisia
• Collaborators: Poseidon CRO
• Investigators: Principal Investigator: Imed Frikha, MD, STCCV

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2019
• Primary Completion (Anticipated): December 30, 2019
• Study Completion (Anticipated): March 30, 2020

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2019
• Last Update Submitted That Met QC Criteria: November 28, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Cyclooxygenase Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticoagulants; Atorvastatin; Captopril; Acetylsalicylic acid lysinate; Glucuronyl glucosamine glycan sulfate; Angiotensin-Converting Enzyme Inhibitors; Platelet Aggregation Inhibitors
• Other Study ID Numbers: AP 12016 AW TN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No