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

Sponsor

Alfa Wassermann Tunisia (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03370705

Collaborator

Poseidon CRO (Industry)

156

Enrollment

Locations

Arms

13.9

Anticipated Duration (Months)

Patients Per Site

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Obstructive Disease	Drug: Sulodexide Drug: Statin Drug: Antiplatelet Agents Drug: ACE inhibitor	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized Multicentric open-label controlled trialRandomized Multicentric open-label controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 31, 2019

Anticipated Primary Completion Date :

Dec 30, 2019

Anticipated Study Completion Date :

Mar 30, 2020

Arms and Interventions

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: Sulodexide Sulodexide 250 ULS twice daily per oral route Other Names: Vessel 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

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: Sulodexide

Sulodexide 250 ULS twice daily per oral route

Other Names:

Vessel

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

Outcome Measures

Primary Outcome Measures

Change from baseline endothelial function after 6 months [between base line (day 1) and day 180]
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).

Secondary Outcome Measures

Metric change of the walking distance [base line, day 90 and day 180:]
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.
Change in Von Willebrand Factor (VWF) level [base line, day 90 and day 180]
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
Assessment of the study medication observance patient's compliance [180 days]
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.
Assessment of safety [180 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.