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.

Study Overview

• Status: Completed
• Conditions: Venous Insufficiency
• Intervention / Treatment: Drug: Diosmin; Drug: Diosmin / Hesperidin

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Teresópolis, RJ, Brazil, 25964004
      • Centro Universitário Serra dos Órgãos - UNIFESO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diosmin; Diosmin 600mg, one tablet once daily	Drug: Diosmin; Diosmin 600mg tablet, once daily
Active Comparator: Diosmin + Hesperidin; Diosmin 900mg + Hesperidin 100mg, one tablet once daily	Drug: Diosmin / Hesperidin; Diosmin 900 mg / Hesperidin 100mg tablet, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VAS symptom scores	Change between the 100mm visual analog scale (VAS) symptoms (from 0mm [absence of venous symptoms] to 100mm [maximal intensity of venous symptoms] scores at month 0 (pretreatment) and month 6 / end of study visit (early withdrawal).	From pretreatment (month 0) until month 6 of the 6-month treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Evolution of VAS score at each visit	Evolution of the 100mm VAS symptoms (from 0mm [absence of venous symptoms] to 100mm [maximal intensity of venous symptoms]) at each visit	From pretreatment (month 0) until month 6 of the 6-month treatment period
Efficacy: Patient global satisfaction at each visit	Evaluation of the patient's global satisfaction at each visit on a four level scale of "bad", "acceptable", "good", and "very good"	From pretreatment (month 0) until month 6 of the 6-month treatment period
Oral acceptability	Evaluation of the oral acceptability on a 100mm VAS (from 0mm - very easy to swallow to 100mm - very difficult to swallow) of the treatment at each visit	From pretreatment (month 0) until month 6 of the 6-month treatment period
Tolerance: Number of related adverse events during the study	Number of related adverse events during the study	Throughout the 6-month treatment period
Efficacy: Investigator's global satisfaction at each visit	Evaluation of the investigator's global satisfaction at each visit on a four level scale of "bad", "acceptable", "good", and "very good"	From pretreatment (month 0) until month 6 of the 6-month treatment period

Collaborators and Investigators

• Sponsor: Fundação Educacional Serra dos Órgãos
• Investigators: Principal Investigator: Marcio Steinbruch, MD, Hospital Albert Einstein; Principal Investigator: Renato Kaufman, MD, Universidade Estadual do Rio de Janeiro

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Actual): March 20, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Hesperidin; Diosmin; Chronic venous insufficiency
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Venous Insufficiency
• Other Study ID Numbers: DIVC-01-12-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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