Clinical Non-inferiority Study Between Diosmin 600mg & Diosmin + Hesperidin in Symptomatic Chronic Venous Insufficiency

Clinical Non-inferiority Study Between Diosmin 600 mg Tablets and Diosmin 900 mg + Hesperidin 100 mg Tablets in Symptomatic Chronic Venous Insufficiency After 6 Months of Treatment: Single-blind, Randomized, Parallel Group Study

Clinical non-inferiority study between Diosmin 600 mg tablets and Diosmin 900 mg + Hesperidin 100 mg tablets in symptomatic chronic venous insufficiency after 6 months of treatment. Prospective, single-blind, randomized study in parallel groups (total patient population 120, 60 subjects per treatment group), with a total of 4 clinical assessment at months 0, 2, 4, and 6 of treatment.

The primary study objective is to demonstrate the clinical non inferiority of efficacy between Diosmin 600 mg tablets versus combination Diosmin 900 mg + Hesperidin 100 mg tablets in improving lower limb symptoms assessed by a 100 mm visual analogue scale (VAS) over 6 months among adult patients presenting chronic venous insufficiency of the lower limbs.

The secondary study objectives are to compare between Diosmin 600 mg tablets and combination Diosmin 900 mg + Hesperidin 100 mg tablets in terms of:

• The oral acceptability,
• The tolerability,
• The global patient's satisfaction,
• The global physician's satisfaction.

Clinical assessments will take place at the study center during the study visits at M0, M2, M4 and M6 including:

• Efficacy on venous symptoms : The VAS of 100 mm is rated by the patient from "0" = Absence of venous symptoms up to "100" = Maximal intensity of the venous symptoms. The VAS is completed by the patient at the investigator's office. This VAS globally assesses the venous symptomatology of the most symptomatic leg : Heavy legs, Painful legs, Tired legs, Sensation of swelling and/or tension in the legs).
• Acceptability : Easiness to swallow assessed by a VAS of 100 mm rated by the patient from "0" = Very easy to swallow, up to "10" = Very difficult to swallow
• Patient's global satisfaction related to the treatment efficacy : Four levels scale rated as following : bad, acceptable, good, and very good
• Investigator's global satisfaction related to the treatment efficacy : Four levels scale rated as following : bad, acceptable, good, and very good
• Tolerability (related adverse events)
• Compliance : Accountability of treatments returned by the patient

The primary endpoint will be the change between the VAS symptoms scores at M0 and M6 / end of study visit (early withdrawal). Secondary endpoints include assessments of efficacy, oral acceptability of study drug, and tolerance.

Inclusion Criteria:

• Patients of both genders >18 years old
• Patient presenting a C0 to C3 venous disease grade of the lower limbs, according to the clinical component of the CEAP classification,
• Clinical symptoms of chronic venous insufficiency of the lower limbs as defined by a VAS of 100 mm rated by the patient between 20 mm and 60 mm on the most symptomatic leg. The VAS is a global evaluation of the following symptoms: Heavy legs, Painful legs, Tired legs, Sensation of swelling and / or tension in the legs.
• Premenopausal female subjects not pregnant or breastfeeding, in use of reliable contraceptive
• Subject has read, understood, dated and signed the informed consent form

Exclusion Criteria:

• Treatment by compression stocking within the 2 months before inclusion
• Treatment by venotonics within the 2 months before inclusion
• Premenopausal women who are pregnant, breastfeeding or who do not wish to use contraception during the study period
• Known allergy or hypersensitivity to any component of the study drug
• Known clinically significant laboratory alterations
• CEAP levels 4, 5 & 6
• Patient with venous disease requiring surgery / chemical endovenous sclerotherapy
• Patient suffering from a painful pathology other than the venous pain in the lower limbs
• Patient with history of venous thrombosis or thromboembolic disease within the 6 months before inclusion
• Patient with alteration of general condition incompatible with his / her participation in the trial
• Patient wishing to be pregnant in the 6 following months