Venoactive Drug Treatment of Pelvic Venous Disorders

NCT06584799 | Recruiting Phase 3

• 1 other identifier: 20452024
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Venoactive drug (VAD) therapy is one of the most effective methods of treating chronic venous diseases (CVD). Numerous studies have proven its high efficacy in relieving symptoms of CVD, such as leg pain and swelling, leg heaviness and fatigue. Pelvic venous disorders (PeVDs) represent a group of pathological conditions including varicose veins of the pelvis and vulva, and compression stenoses of the left renal and common iliac veins. Although PeVDs are associated with venous lesions of the pelvis and retroperitoneum and have specific clinical manifestations, they are one of the forms of CVD and constitute a separate cohort. A number of studies on the VAD usage in PeVD indicate the wide possibilities of this type of treatment in eliminating chronic pelvic pain (CPP), the most dramatic symptom of PeVD, which is the main cause of disability and decreased quality of life, social and daily activity in women with PeVD. Currently, a variety of VADs are presented on the pharmaceutical market, which, according to the product labels, provide effects not only on the venous outflow from the lower extremities, but also on venous hemodynamics in the pelvis. At the same time, a literature analysis shows that micronized purified flavonoid fraction (MPFF) has the greatest evidence base obtained in the efficacy and safety studies of VADs in PeVD. Nevertheless, patients are rarely interested in the scientific dossier of drugs, and in the real practice the patients with PeVD and CPP most often ask: "What is the best drug to use for the CPP relief?" This is quite understandable, as it is CPP in PeVD that results not only in disability, but also in family conflicts, psycho-emotional stress and depressive states. In this regard, patients seek to get rid of pain as soon as possible and strive to use the most effective drug. An extensive scientific base of comparative studies on the use of various VADs in patients with CVD and PeVD has been accumulated to date. However, the literature is lack of any data on the comparative efficacy and safety of VADs in the treatment of patients with PeVD. This, in turn, makes not possible for doctors and patients to choose the optimal and most effective drug based on the objective research data. All the above has predetermined the purpose of the planned study as evaluating the efficacy and safety of different VADs in the treatment of female patients with PeVD.

Conditions

Pelvic Venous Disorders

Keywords

pelvic venous disorders; chronic pelvic pain; venoactive drug therapy; pelvic pain

Outcome Measures

Primary Outcomes (1)

• Severety of the chronic pelvic pain

  Evaluation of the efficacy of venoactive drug treatment on chronic pelvic pain by using visual analogue scale

  Every weekly until 8 weeks

Secondary Outcomes (1)

• Side and adverse effects

  during the treatment until 8 weeks

Study Arms (3)

Group 1

ACTIVE COMPARATOR

Group will include 50 patients, which will be treated by MPFF 1000 mg once daily for 2 months

Drug: Micronized purified flavonoid fraction

Group 2

ACTIVE COMPARATOR

Group will include 50 patients which will be treated by Diosmin 600 mg once daily for 2 months

Drug: Diosmin 600

Group 3

ACTIVE COMPARATOR

Group will include 50 patients which will be treated by combination Hespiridin+Diosmin 1000 mg once daily for 2 months

Drug: Hesperidin+Diosmin combination 1000

Interventions

Micronized purified flavonoid fraction DRUG

Micronized purified flavonoid fraction (MPFF) 1000. Active substance: micronized purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin). MPFF is a venotonic agent that also has angioprotective properties. It reduces venous distensibility and blood stasis, capillary permeability, and increases capillary resistance. MOFF 1000 dosing regimen is 1000 mg once daily for 2 months.

Group 1

Diosmin 600 DRUG

Venotonic action: the drug reduces venous distensibility, increases venous tone, reduces blood stasis, and enhances the vasoconstrictor effect of epinephrine and norepinephrine. The optimal daily dose of diosmin 600 for obtaining venotonic effect is 600 mg.

Group 2

Hesperidin+Diosmin combination 1000 DRUG

A venotonic agent that also has angioprotective properties. It reduces venous distensibility and blood stasis, reduces capillary permeability and increases their resistance. Hesperidin+Diosmin combination 1000 dosing regimen is 1000 mg once daily for 2 months

Group 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age from 18 to 45 years;
• The presence of PeVD symptoms (CPP, dyspareunia, discomfort in the hypogastrium, dysuria, vulvar varicose veins);
• The presence of pelvic varicose veins with reflux in them, according to DUS;
• Pelvic venous reflux (PVR) lasting for greater than 1 s, according to DUS;
• Isolated dilation and reflux in the parametrial and uterine veins, according to DUS;
• Absence of competing abnormalities, accompanied by CPP.

You may not qualify if:

• Asymptomatic form of the disease;
• Menopause;
• Pregnancy;
• Post-thrombotic disease;
• Neoplasms;
• Competing diseases with CPP;
• Known hypersensitivity to any of the components of the used VAD.

Sponsors & Collaborators

• Pirogov Russian National Research Medical University: lead

Study Sites (1)

Pirogov Russian National Research Medical University

Moskva, 117513, Russia

RECRUITING

Related Publications (8)

• Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.

  PMID: 33141449 BACKGROUND

• De Maeseneer MG, Kakkos SK, Aherne T, Baekgaard N, Black S, Blomgren L, Giannoukas A, Gohel M, de Graaf R, Hamel-Desnos C, Jawien A, Jaworucka-Kaczorowska A, Lattimer CR, Mosti G, Noppeney T, van Rijn MJ, Stansby G, Esvs Guidelines Committee, Kolh P, Bastos Goncalves F, Chakfe N, Coscas R, de Borst GJ, Dias NV, Hinchliffe RJ, Koncar IB, Lindholt JS, Trimarchi S, Tulamo R, Twine CP, Vermassen F, Wanhainen A, Document Reviewers, Bjorck M, Labropoulos N, Lurie F, Mansilha A, Nyamekye IK, Ramirez Ortega M, Ulloa JH, Urbanek T, van Rij AM, Vuylsteke ME. Editor's Choice - European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs. Eur J Vasc Endovasc Surg. 2022 Feb;63(2):184-267. doi: 10.1016/j.ejvs.2021.12.024. Epub 2022 Jan 11. No abstract available.

  PMID: 35027279 BACKGROUND

• Nicolaides A, Kakkos S, Baekgaard N, Comerota A, de Maeseneer M, Eklof B, Giannoukas AD, Lugli M, Maleti O, Myers K, Nelzen O, Partsch H, Perrin M. Management of chronic venous disorders of the lower limbs. Guidelines According to Scientific Evidence. Part I. Int Angiol. 2018 Jun;37(3):181-254. doi: 10.23736/S0392-9590.18.03999-8. No abstract available.

  PMID: 29871479 BACKGROUND

• Antignani PL, Lazarashvili Z, Monedero JL, Ezpeleta SZ, Whiteley MS, Khilnani NM, Meissner MH, Wittens CH, Kurstjens RL, Belova L, Bokuchava M, Elkashishi WT, Jeanneret-Gris C, Geroulakos G, Gianesini S, de Graaf R, Krzanowski M, Al Tarazi L, Tessari L, Wikkeling M. Diagnosis and treatment of pelvic congestion syndrome: UIP consensus document. Int Angiol. 2019 Aug;38(4):265-283. doi: 10.23736/S0392-9590.19.04237-8. Epub 2019 Jul 24. No abstract available.

  PMID: 31345010 BACKGROUND

• Simsek M, Burak F, Taskin O. Effects of micronized purified flavonoid fraction (Daflon) on pelvic pain in women with laparoscopically diagnosed pelvic congestion syndrome: a randomized crossover trial. Clin Exp Obstet Gynecol. 2007;34(2):96-8.

  PMID: 17629162 BACKGROUND

• Akhmetzianov RV, Bredikhin RA. Clinical Efficacy of Conservative Treatment with Micronized Purified Flavonoid Fraction in Female Patients with Pelvic Congestion Syndrome. Pain Ther. 2021 Dec;10(2):1567-1578. doi: 10.1007/s40122-021-00312-6. Epub 2021 Sep 19.

  PMID: 34537951 BACKGROUND

• Gavrilov SG, Moskalenko YP, Karalkin AV. Effectiveness and safety of micronized purified flavonoid fraction for the treatment of concomitant varicose veins of the pelvis and lower extremities. Curr Med Res Opin. 2019 Jun;35(6):1019-1026. doi: 10.1080/03007995.2018.1552043. Epub 2018 Dec 20.

  PMID: 30468077 BACKGROUND

• Gavrilov SG, Moskalenko YP, Grishenkova AS, Chubchenko SV. Venoactive drug treatment for patients with pelvic varicose veins: Results of the single-center, randomized, open-label study (VENOTREAT). Vasc Med. 2025 Oct;30(5):590-598. doi: 10.1177/1358863X251362200. Epub 2025 Aug 25.

  PMID: 40855727 DERIVED

Related Links

• General information about micronized purified flavonoid fraction 1000
• General information about Diosmin 600

MeSH Terms

Conditions

Pelvic Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anatoly V Karalkin, MD, PhD

  Pirogov Russian National Research Medical University

  STUDY CHAIR

Central Study Contacts

Sergey G Gavrilov, MD, PhD

CONTACT

89169299947; gavriloffsg@mail.ru

Alexander V Alenichev

CONTACT

89262921111; alenichev@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Sealed envelope principle
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Clinical trials with a single arm. The study will include 150 consecutive female patients with symptomatic PeVD. All patients will undergo a clinical examination, transabdominal and transvaginal DUS of the pelvic veins to verify the diagnosis and to determine the diameters of the pelvic veins and the duration of reflux in them. The CPP intensity will be assessed using a visual analogue scale (VAS). For randomization procedure, the sealed envelope principle will be used. Three groups of 50 patients each will be formed depending on the recommended VAD usage: group 1 (n=50) with MPFF1000; group 2 (n=50) with Diosmin 600; and group 3 (n=50) with Hesperidin + Diosmin 1000. After the start of VAD intake, the patients will be self-rating the pain intensity on VAS on the weekly basis. Based on the repeated examination data and the VAS results, a comparative analysis of the clinical efficacy of VADs will be carried out.

Study Record Dates

• First Submitted: August 29, 2024
• First Posted: September 5, 2024
• Study Start: December 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: February 1, 2025
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)