Clinical trial NCT03471910: Clinical Non-inferiority Study Between Diosmin 600mg & Diosmin + Hesperidin in Symptomatic Chronic Venous Insufficiency
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Venous Insufficiency
Keywords: Chronic venous insufficiency
Diosmin
Hesperidin
Lead sponsor: Fundação Educacional Serra dos Órgãos
Sponsor class: OTHER
First posted: 2018-03-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in VAS symptom scores
timeFrame: From pretreatment (month 0) until month 6 of the 6-month treatment period
Secondary outcomes:
measure: Efficacy: Evolution of VAS score at each visit
timeFrame: From pretreatment (month 0) until month 6 of the 6-month treatment period
measure: Efficacy: Patient global satisfaction at each visit
timeFrame: From pretreatment (month 0) until month 6 of the 6-month treatment period
measure: Oral acceptability
timeFrame: From pretreatment (month 0) until month 6 of the 6-month treatment period
measure: Tolerance: Number of related adverse events during the study
timeFrame: Throughout the 6-month treatment period
measure: Efficacy: Investigator's global satisfaction at each visit
timeFrame: From pretreatment (month 0) until month 6 of the 6-month treatment period
Other outcomes:
Locations:
city: Teresópolis
country: Brazil
facility: Centro Universitário Serra dos Órgãos - UNIFESO
state: RJ
Study officials:
affiliation: Hospital Albert Einstein
name: Marcio Steinbruch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Estadual do Rio de Janeiro
name: Renato Kaufman, MD
role: PRINCIPAL_INVESTIGATOR
References: