Study of Venous Outflow From the Lower Limbs in Patients With Pelvic Varicosities as a New Strategy for Compression Treatment of Pelvic Varicose Veins and Varicose Veins of the Lower Limb
Conditions: Pelvic Varices, Varicose Veins of Lower Limb, Pelvic Pain Syndrome, Pelvic Congestive Syndrome
Sponsor: Pirogov Russian National Research Medical University

 
 
Clinical Study protocol: «Study of venous outflow from the lower limbs in patients with 
pelvic varicosities as a new strategy for compression treatment of pelvic varicose veins and 
varicose veins of the lower limb» 
 
NCT: no 
Date: May 4, 2023 
 
Compression therapy is basic treatment for chronic venous disease (CVD) of the lower 
limbs. Numerous studies have demonstrated the efficacy and safety of compression therapy in 
relieving symptoms such as pain, venous edema, leg heaviness and fatigue, as well as accelerating 
the healing of venous ulcers. It has been established that сompression therapy is indicated for 
patients with both minimally expressed manifestations of CVD and severe forms of the disease. 
At the same only one study has been conducted to assess the correction of venous outflow from 
the lower limbs and pelvis in patients with pelvic varicose vein (PVV) and pelvic congestion 
syndrome (PCS). However, the incidence of this pathology ranges from 15 to 30% in the female 
population. The cost to the healthcare system of treating these patients in the United States exceeds 
$2 billion. To date, the options and indications for compression therapy in patients with 
concomitant PVV and CVD have not been defined. The rational use of compression in this cohort 
of patients may contribute to the improvement of effective conservative treatment. In addition, 
inappropriate prescription of compression to patients with pelvic venous disease (which can be 
observed in real clinical practice) may discredit this simple, effective and safe therapeutic method. 
In addition, the research devoted to the problem of compression treatment of PVV will contribute 
to the development of new special compression products aimed at accelerating venous outflow 
from the pelvic organs. It can be assumed that this will serve as a stimulus for obtaining new data 
on the therapeutic effects of compression and create conditions for the creation of new 
technological directions in the production of compression knitwear. 
Aim: To study the venous outflow disturbance of the lower limbs in patients with PVV and 
to develop a new compression treatment strategy for patients with PVV and CVD. 
Study goal: 
 To study the status of venous outflow from the lower limbs and pelvis in patients with 
concomitant PVV and CVD.; 
 To identify correlations between the degree of impairment of venous outflow from the 
pelvis and the severity of impairment of the lower extremity musculo-venous pump 
(MVP) as the main peripheral determinant of venous return from the lower limbs.; 
 To study the influence of the duration and extent (involvement in the pathological 
process) of pelvic venous reflux on the degree of venous outflow disturbance of the lower 
limbs; 
 To develop ultrasound and radionuclide criteria for the severity of pelvic congestion 
syndrome; 

 
 
 To study the possibility of using the coefficient of pelvic congestion syndrome (Cpcs) as 
a predictor of venous outflow disturbance of the lower limbs; 
 To establish the criteria for correcting venous outflow disturbances in the lower limbs 
with compression based on the severity of pelvic congestion syndrome; 
 To evaluate the effectiveness of compression therapy for CVD in patients with PVV 
(PCS) and impaired venous outflow from the lower extremities and the musculo-venous 
pump function. 
Material and methods.  
This study enrolled 90 female patients, including 40 patients with PVV and PCS, 40 patients 
with combined PVV and CVD, and 10 patients with CVD without pelvic vein pathology. 
 
Clinical study:  
All patients undergo examination by a physician-researcher who documents patient complaints, 
medical history, and physical examination findings in individual medical records. Chronic pelvic 
pain (CPP) and pain in the lower limbs will be assessed with a visual analog scale (VAS), which 
is a horizontal line 10 cm long, with each centimeter representing 1 point. The severity of pain on 
the VAS is estimated as follows: 0 points - no pain; 1-3 points - mild pain; 4-6 points - medium 
pain; 7-8 points - severe pain; 9-10 points - worst pain. 
Diagnostics: 
Duplex ultrasound (DUS) of the lower limb veins will be performed on all patients. 
Transabdominal and transvaginal  DUS will be performed on all 90 patients, too. Radionuclide 
venography of the left or right lower limbs (depending on the side of the lesion) will be  also 
performed in all patients. Additionally, the single-photon emission computed tomography 
(SPECT) of the pelvic veins with in vivo-labelled red blood cells (RBCs) will be performed in all 
patients (n=90). 
Treatments: 
Compression therapy with either class 1 or class 2 compression stockings will be administered to 
90 patients with PVD and/or CVD. The selection of the compression class was based on the CEAP 
class and the severity of tibial MVP abnormalities according to radiophlebography data. The 
researcher will select the size of the compression product according to the standard scheme after 
verifying the diagnosis by pelvic and lower extremity vein DUS and radionuclide assessment of 
venous outflow from the pelvic and lower extremity veins (radionuclide venography and SPECT). 
General information 
Title: «Study of venous outflow from the lower limbs in patients with pelvic varicosities as a new 
strategy for compression treatment of pelvic varicose veins and lower limb varicose vein disease» 

 
 
Responsible for the study: Sergey G. Gavrilov, MD, Professor, Pirogov Russian National Research 
Medical University. N.I. Pirogov Russian National Research Medical University, 117997, 
Moscow, 1 Ostrovityanova St., tel: 8 (495) 434-30-83. 
Division: Savelyev University Surgical Clinic, 119049, Moscow, Leninsky Prospekt, 10/5, office 
0076. 
Rationale and basic information/ Abstract 
Currently, the term "varicose veins" implies not only the pathology of the superficial veins of the 
lower limbs, but also the pelvic veins. As yet, no epidemiological studies have investigated the 
frequency of the combination of pelvic and lower limb varicose veins, but in some studies the 
authors point to a combination of lower limb varicose veins and pelvic varicose veins (PVV) in 
30-60% of patients. In this scenario, we are discussing the disease's clinically manifested forms, 
where lower limb varicose veins are visually identified and pelvic veins are identified by 
ultrasound and manifest as symptoms of pelvic congestion syndrome. There is no evidence of a 
concomitant occurrence of asymptomatic or latent forms of varicose veins in the lower limbs and 
PVV. (In this cases during duplex ultrasound angioscanning (DUS), pathological blood reflux is 
detected in the dilated superficial veins of the lower limbs and pelvis. However, there are no 
symptoms or signs of the disease.) As a result, it is not possible to assess the true prevalence of 
the combination of CVD and PVV. 
At the same time, it is evident that dilatation and reflux in pelvic veins cannot but affect the clinical 
course of CVD in general and lower limb varicose vein disease in particular.  Multiple studies 
from our clinic and foreign colleagues have substantiated this claim. It is caused not only by 
anatomical links between pelvic veins and lower limbs (perineal, clitoral perforating veins, 
tributaries of internal iliac veins), but also by common triggering mechanisms and similar 
pathogenesis of lower limb varicose vein disease and PVV.  
Considering the above, valid questions arise about the effect of pelvic varicose veins with reflux 
on lower extremity venous outflow: 
1. How does asymptomatic pelvic vein dilation with reflux impact venous outflow from the 
lower extremities and the clinical manifestations of CVD? 
2. Does symptomatic pelvic vein dilation with reflux affect venous outflow from the lower 
limbs and clinical manifestations of CVD?  
3. Does vulvar vein dilation affect venous outflow from the lower limbs and CVD clinical 
manifestations?  
4. Is the severity or exposure of pelvic congestion syndrome a predictor for the development 
of lower limb venous outflow disorders?  
5. How does the severity of clinical manifestations of PCS correspond to the severity of 
hemodynamic disturbance, as determined through instrumental research methods? 
These questions have significance not only in academic and scientific domains. They are directly 
related to the strategy and tactics of treating patients with a combination of varicose veins of 

 
 
lower limbs and PVV, PCS and CVD, since the following fundamental issues have not yet been 
resolved: 
1. Do asymptomatic patients with instrumental detection of PVV and lower limb varicose 
vein require correction? 
2. Is it appropriate to utilize compression knitwear in patients with an asymptomatic course 
of instrumentally confirmed venous outflow disorders with a combination of pelvic and 
lower extremity varicose veins? 
3. Can the coefficient of pelvic venous congestion be utilized as a quantitative indicator to 
prescribe compression treatment for venous outflow disorders in the lower limbs of 
asymptomatic patients without signs of CVD? In other words, can the coefficient of pelvic 
venous congestion be used as a reference index for correcting the evacuative function of 
the tibial MVP in patients without clinical manifestations of CVD? 
4. How effective is compression in correcting impaired venous outflow from the lower 
limbs in PVV patients?  
The severity of the clinical course of lower limb CPV is determined by objective symptoms such 
as pain, edema, trophic disorders, and venous ulceration. In patients with CVD, the severity of 
the disease course determines the development of pelvic congestion syndrome (PCS), which is 
manifested by chronic pelvic pain (CPP), hypogastric heaviness, and dyspareunia. CPP and 
dyspareunia are the main indicators of the severity of the clinical course of PCS. It has been 
demonstrated that PCS exacerbates the symptoms of CVD. Thus, correlating the severity of 
pelvic pain to the degree of pelvic venous fullness (coefficient calculated by pelvic venous 
scintigraphy) allows us to assume the presence of venous outflow disorders of the lower 
extremities. According to this hypothesis, the presence and severity of venous outflow disorders 
of the lower limbs can be determined not only by the results of instrumental examination of the 
pelvic and limb veins, but also by clinical assessment of the severity of CPP. 
 
Reference 
1. 
Partsch H. Compression for the management of venous leg ulcers: which material do we 
have? Phlebology 2014(1 suppl):140-145. 
2. 
Vin F, Benigni JP. Compression therapy. International Consensus Document Guidelines 
according to scientific evidence. Int Angiol 2004;23:317-345. 
3. 
Partsch H, Clark M, Mosti G, Steinlechner E, Schuren J, Abel M, et al. Classification of 
compression bandages:practical aspects. Dermatol Surg 2008;34:600-609. 
4. 
Keller A, Müller ML, Calow T, Kern IK, Schumann H. Bandage pressure measurement 
and training: simple interventions to improve efficacy in compression bandaging. Int Wound J 
2009;6:324-30. 
5. 
Amsler F, Blättler W. Compression therapy for occupational leg symptoms and chronic 
venous disorders - a meta-analysis of randomised controlled trials. Eur J Vasc Endovasc Surg. 
2008;35(3):366-372. https://doi.org/10.1016/j.ejvs.2007.09.021  

 
 
6. 
Nicolaides, A., Kakkos, S., Eklof, B., Perrin, M., Nelzen, O., Neglen, P., Partsch, H., 
Rybak, Z. Management of chronic venous disorders of the lower limbs - guidelines according to 
scientific evidence. International angiology 2014. 33(2), 87–208. 
7. 
Russian Clinical Guidelines for the Diagnostics and Treatment of Chronic Venous 
Diseases. 
Flebologiya. 
2018;12(3):146‑240. 
(In 
Russ.) 
https://doi.org/10.17116/flebo20187031146 
8. 
Wu X, Liu R, Lao TT. Therapeutic compression materials and wound dressings for chronic 
venous insufficiency: A comprehensive review. J Biomed Mater Res B Appl Biomater. 
2020;108(3):892-909. https://doi.org/10.1002/jbm.b.34443  
9. 
Gavrilov, S.G., Karalkin, A.V., Turischeva, O.O. Compression treatment of pelvic 
congestion syndrome. Phlebology. 2018;33: 418-424. https://doi.org/10.1177/0268355517717424  
10. 
Mathias, S.D., Kuppermann, M., Liberman, R.F., et al. Chronic pelvic pain: prevalence, 
health-related quality of life, and economic correlates. Obstet Gynecol. 1996; 87:321–327 
11. 
Kuligowska, E., Deeds, L., Lu, K. Pelvic pain: overlooked and underdiagnosed 
gynecologic conditions. Radiographics. 2005:25; 3–20. 
12. 
Olson, C., Schnatz, P.F. Evaluation and management of chronic pelvic pain in women. J 
Clin Outcomes Manage. 2007;4:563-574. 
13. 
Latthe P, Latthe M, Say L, et al. WHO systematic review of prevalence of chronic pelvic 
pain: a neglected reproductive health morbidity. BMC Public Health. 2006;6: 177. 
14. 
Gavrilov SG, Moskalenko YP. Does pelvic congestion syndrome influence symptoms of 
chronic venous disease of the lower extremities? Eur J Obstet Gynecol Reprod Biol. 2019;243:83-
86. https://doi.org/10.1016/j.ejogrb.2019.10.025  
15. 
Gavrilov SG, Moskalenko EP, Efremova OI. Does Intrapelvic Veins Enlargement 
Influence Symptoms of Chronic Venous Disease in Patientswith Concomitant Varicose Veins of 
Pelvis 
and 
Lower 
Extremities? 
Flebologiya. 
2019;13(2):112‑118. 
(In 
Russ.) 
https://doi.org/10.17116/flebo201913021112. 2019;13(2):112-118 
16. 
Gavrilov S.G., Moskalenko E.P., Efremova O.I. Pelvic venous congestion aggravates the 
symptoms of chronic venous insufficiency. RMJ. 2018;26(6-2):65-69. (In Russ) 
17. 
Pokrovsky A.V., Ignatiev I.M., Bredikhin R.A., Gradusov E.G. Postoperative recurrence 
of varicose veins. Angiology and vascular surgery. 2015;21(4):118-125 (In Russ) 
18. 
Gültaşli NZ, Kurt A, Ipek A, Gümüş M, Yazicioğlu KR, Dilmen G, Taş I.The relation 
between pelvic varicose veins, chronic pelvic pain and lower extremity venous insufficiency in 
women. Diagn Interv Radiol. 2006 Mar;12(1):34-38. 
19. 
Whiteley AM, Taylor DC, Dos Santos SJ, Whiteley MS. Pelvic venous reflux is a major 
contributory cause of recurrent varicose veins in more than a quarter of women. J Vasc Surg 
Venous Lymphat Disord. 2014;2(4):411-415. https://doi.org/10.1016/j.jvsv.2014.05.005  

 
 
20. 
Asciutto G, Mumme A, Asciutto KC, Geier B. Pelvic vein incompetence influences pain 
levels 
in 
patients 
with 
lower 
limb 
varicosity. 
Phlebology. 
2010;25(4):179-183. 
https://doi.org/10.1258/phleb.2009.009014 
21. 
Foong LC, Gamble J, Sutherland IA, Beard RW. Altered peripheral vascular response of 
women with and without pelvic pain due to congestion. BJOG. 2000 Feb;107(2):157-164. 
https://doi.org/10.1111/j.1471-0528.2000.tb11684.x    
22. 
Bora A, Avcu S, Arslan H, Adali E, Bulut MD. The relation between pelvic varicose veins 
and lower extremity venous insufficiency in women with chronic pelvic pain. JBR-BTR. 
2012;95(4):215-221. 
23. 
Kirienko A.I., Gavrilov S.G., Karalkin A.V., Butenko O.V., Kapranov S.A., Novikov S.A. 
Diagnosis of varicose veins of the pelvis. Annals of surgery. 2003;4:51-56 (In Russ) 
24. 
Gavrilov SG, Turischeva OO. Conservative treatment of pelvic congestion syndrome: 
indications 
and 
opportunities. 
Curr 
Med 
Res 
Opin. 
2017;33:1099-1103. 
https://doi.org/10.1080/03007995.2017.1302414 
Objectives of the study 
To examine the correlation between impaired venous outflow from the pelvis and venous 
outflow from the lower limbs, to identify predictors of impaired venous outflow from the lower 
limbs in patients with PVV without clinical manifestations of CVD, to determine indications for 
the use of compression therapy of the lower limbs in patients with PVV but without symptomatic 
CVD based on the severity of disturbances in venous outflow from the pelvis. 
Primary endpoint of the study  
To investigate the impact of varicose veins of the pelvis and pelvic congestion syndrome on the 
venous outflow of the lower limbs and the function of the muscular-venous pump of the lower 
limbs. 
 Secondary endpoint of the study  
To assess the efficacy and comfort of utilizing compression stockings of class 1 and 2 in the 
treatment of lower limbs venous outflow disorders and correction of lower limb muscular-venous 
pump dysfunction in patients with PCS in combination with subclinical and clinically manifested 
lower limb CVD. 
Study design  
This is a single-center, prospective, comparative cohort study. The duration of the study is from 
1/4/2023 to 1/12/2023. The study includes 90 patients (40 patients with symptomatic PVV without 
CVD, 40 patients with asymptomatic PVV and symptoms of CVD, 10 patients with lower limb 
varicose vein disease (CVD) without PVV.  
Inclusion criteria:  
• Patient age group: 18-40 years;  
• Presence of pelvic varicose veins according to DUS data;  

 
 
• Reflux in the pelvic veins for more than 1 second before this DUS;  
• Reflux in the superficial veins of the lower limbs. 
Exclusion criteria: 
• Menopause;  
• Pregnancy;  
• Postthrombotic syndrome;  
• Suspicion of May-Turner syndrome;  
• Ultrasound signs of nutcracker syndrome.  
Before being included in the study, every patient signs a voluntary informed consent form to 
participate in the research. 
The study enrolled 90 female patients, including 80 patients with PVV and 10 patients with CVD 
without PVV. All patients undergo a physician examination and receive DUS of pelvic veins and 
lower limbs, regardless of the presence or absence of clinical manifestations of diseases of pelvic 
veins and lower limbs. Then the patients are classified into three groups based on clinical and 
ultrasound evaluation. The first group (n=40) comprises patients with symptomatic PVV, 
including pelvic pain, dyspareunia, and heaviness in the hypogastrium, but without symptoms or 
signs of CVD. The second group (n=40) consists of women with asymptomatic PVV but with 
indications of CVD. The third group consists of 10 patients with varicose veins in the lower limb, 
without PVV or PCS symptoms. All patients undergo radionuclide venography of the lower limbs 
and emission computed tomography (SPECT) of the pelvic veins with in vivo labelled red blood 
cells (RBC). Quantitative indicators of the function of the lower extremity muscle-venous pump 
(MVP) and the pelvic venous congestion syndrome coefficient (Cpvc) are objectively assessed, 
using the results of radionuclide venography and single-photon emission computed tomography 
(SPECT). These indicators include average radiopharmaceutical transport time from regions of 
interest, and objectively represent blood venous flow from the veins of the lower extremities and 
the pelvis. Compression treatment using class 1 or 2 stockings is prescribed for patients with 
impaired venous outflow from the lower limbs and impaired venous evacuation function of the 
lower leg vein duct, depending on the class of CVD according to CEAP. Follow-up examinations, 
including clinical evaluations and radionuclide studies with SPECT of the pelvic veins, are 
performed 10 days after the initial clinical examination and radionuclide phlebography to evaluate 
the efficacy of the compression treatment.  
Radionuclide venography with single-photon emission computed tomography (SPECT) of the 
pelvic veins and repeated clinical examinations are performed to evaluate the efficacy of the 
compression treatment 10 days after the initial clinical examination. Figure 1 displays the study's 
design. 
 
1. A clinical examination comprises of complaints and medical history review, physical 
examination, checking of local vascular status and evaluating pain severity using the visual 

 
 
analogue scale (VAS). VAS aids in identifying the severity of CPP. Additionally, to clinically 
assess the severity of CVD, the Revised Venous Clinical Severity Score (rVCSS) will be 
utilized. The clinical examination is conducted prior to DUS, radionuclide venography, and 
ECT. Then, after ten days of receiving compression treatment, the patients undergo a control 
clinical examination. 
2. Duplex ultrasound scanning (DUS) of the lower limb veins is performed following a clinical 
exam to evaluate patency and status of the valve apparatus in the deep, superficial, and 
perforating veins.  In addition to examining the veins in the limbs, DUS is used to assess the 
condition of the vulvar/perineal veins; 
3. This is followed by transabdominal and transvaginal ultrasound of the pelvic veins, which 
includes assessing the patency of the pelvic, iliac, inferior vena cava and renal veins, measuring 
their diameters, determining the presence of blood reflux through the pelvic veins (gonadal, 
parametrial, uterine). The left renal vein (LRV) condition is analyzed by determining the vessel 
diameter at the point of intersection with the superior mesenteric artery and at the kidney gate. 
Blood flow velocity is measured at these locations, and the ratios of diameters and velocities 
are calculated to evaluate the degree of LRV stenosis. 
4. Radionuclide venography. The procedure is performed using a gamma camera and integrated 
computer. While the patient is upright, 370 MBq of 99mTc pertechnetate is injected into one 
of the dorsal veins of the foot after a tourniquet has been applied in the area of the ankle joint. 
With the assistance of a gamma camera detector, we track the transit of the 
radiopharmaceutical in the tibial (muscular-venous pump of the lower leg), popliteal, femoral, 
and iliocaval segments. During the investigation of the tibial pump, the patient performs 
flexion-extension movements in the ankle joint with a fixed heel to activate the calf pump. The 
gathered data is recorded on the magnetic-optical disk of the computer and then 
mathematically processed. To investigate the evacuation function of the muscular venous 
pump (MVP) of the leg an analytical computer program is used to identify areas of interest in 
the tendon, muscular portions of the leg veins, and the popliteal vein. Then, activity-time 
curves are constructed to estimate the evacuation time of the radiopharmaceutical from the 
MVP of the leg. This provides the average transportation time of the isotope. The average 
isotope transport time is inversely proportional to the volumetric velocity of blood flow. The 
longer the isotope's average transport time, the slower the blood flow velocity through the deep 
veins of the leg, and vice versa.Additionally, the rate of blood flow in the tibial veins is 
measured, providing information on the lower leg's MVP function. Analyzing a panoramic 
image of the veins from the foot to the inferior vena cava allows for an objective evaluation of 
deep vein patency and identification of any venovenous discharges that indicate pathology. 
Normally, only the deep veins in the examined limb are contrasted, while the saphenous and 
perforating veins are not visualized. The activity-time plot identifies the quick escalation and 
decline of isotope activity in the area of concern. The average time required to transport in the 
tendon area of the leg is normally 6-8 s, in the muscle part - 10-12 s, in the popliteal vein - 12-
16 s.  
5. The single-photon emission computed tomography (SPECT) of the pelvic veins with in vivo-
labelled red blood cells (RBCs). In order to assess the status of the pelvic veins with the 
radionuclide, 2 ml of Perfotech solution is injected into the cubital vein for the in vivo 

 
 
labeling of red blood cells. After 20 minutes, 370 MBq of 99mTc-pertechnetate is injected 
into one of the veins on the dorsum of the foot.  Radionuclide venography is performed as 
described above. Twenty minutes after administering the radiopharmaceutical and RFG (the 
necessary time for 99mTc-pertechnetate and autoerythrocytes to bind), single-photon 
emission computed tomography (SPECT) of the pelvic veins is conducted. The patient lies 
horizontally on her back, with the gamma camera detector centered above the womb. In 
order to obtain a tomographic image of the distribution of the labeled erythrocytes in the 
pelvic veins, 32 projections are made in a circular path with the gamma camera detector 
rotated 360°, using a 30-second exposure for each frame. The acquired information is 
analyzed using the SPECT Protocol software package, which generates sections in three 
projections (sagittal, transverse, and coronal) with a slice interval of 8 millimeters. The 
radiopharmaceutical utilized is non-reactive to the venous wall and does not stick to the 
vessels. The labeled red blood cells only amass in regions with heightened blood 
accumulation, such as varicose veins, liver, and spleen. 
Normally, the gonadal veins are not contrasted, with either an absence or slight accumulation of 
radiopharmaceuticals in the pelvis venous plexus. To eliminate potential errors in the assessment 
of pelvic venous stasis, mathematical calculations of areas of interest are utilized due to the 
possibility of weak contrast of intrapelvic veins, caused by low activity of labeled red blood cells 
and errors in radiopharmaceutical administration. The gamma camera's computer equipment 
enables calculation of pulse numbers from the region of interest. The gamma camera captures 
radiopharmaceutical radiation activity in pulses per second, which quantitatively represents the 
content of labeled red blood cells within the region of interest. To ensure the objectivity of 
collected data, a ratio of pulse counts from two standard regions of interest is utilized - the veins 
of the uterus and parametrium, and the common iliac vein on each side. This is necessary as the 
speed of blood flow in pelvic veins can vary between patients. This ratio is known as the pelvic 
venous congestion coefficient (Сpvc). The labeled erythrocyte activity in this vessel remains the 
most stable value, while the activity of erythrocyte-phosphate-pertechnetate complexes in the 
venous plexuses relies on their varicose transformation and blood deposition. Normally, Cpvc 
does not exceed 0.5. An increase in this ratio indicates the presence of pelvic venous congestion 
due to stagnation of blood in the venous plexus of the pelvis. The higher the Cpvc, the more 
pronounced the pelvic venous congestion and stagnation of blood in the pelvic veins. 
6.  Compression treatment. Compression stockings of class 1 and 2 will be utilized as a method 
of compression therapy. The selection of compression class relies on the CVD classification 
as outlined by CEAP and the existence of impairments in the evacuation function of the lower 
extremity MVP in regards to the radiophlebography data of the lower limbs. The patient is 
instructed to wear these stockings for 10 consecutive days, 8 hours daily, following which 
repeated clinical and radionuclide examinations will be conducted to evaluate the efficacy of 
the treatment. The comfort level of the compression socks will be evaluated using a visual 
analog scale. This 10 cm long horizontal line assigns 1 point to each centimeter. Based on 
patient assessments, the following gradations of comfort will be identified: 9-10 points - 
complete absence of discomfort, comfortable wearing of the knitwear for 8 hours or more; 7-
8 points - minor short-term mild discomfort (mild discomfort: a feeling of squeezing, sliding), 
which does not interfere with wearing the knitwear for 8 hours; 4-6 points - average severity 
of discomfort, the patient has difficulties using the stockings for 8 hours; 1-3 points - severe 
degree of discomfort, inability to use compression stockings.  
Data from clinical examinations, ultrasound, and radionuclide studies are documented in the 
patient's personal medical record. 
 
Safety of research and treatment 

 
 
If any side effects or adverse events occur due to the administration of radiopharmaceuticals or 
use of compression products, they are reported and all necessary measures are taken to control 
these side effects and adverse reactions. 
Follow-up 
For a period of two months following the study's conclusion, each patient will undergo monitoring 
in order to identify the presence of any side effects or adverse events. Furthermore, continuous 
assessment of the treatment's efficacy will be conducted during this period. 
Data processing and statistical analysis 
The data of interest are analyzed using the MS Excel program to create summary tables. Statistical 
analysis is performed using MS Excel, Statistica 6.0, and the VassarStats online calculator (open 
source project). The arithmetic mean (M) and standard deviation (SD) were calculated. Qualitative 
variables are compared using Fisher's exact test, and quantitative variables are compared using 
Student's criterion or Mann-Whitney U test, as appropriate. Statistical significance was assumed 
at P value under 0.05. 
Рublication ethics 
The study results will be published in scientific journals, presented at scientific forums and 
conferences, and used for creating methodological recommendations by the Ministry of Health. 
Additionally, information about the study outcomes will be posted on social networks. The leading 
role in the publications will be played by S.G. Gavrilov together with A.V. Karalkin, N.Yu. 
Mishakina, and A.S. Grishenkova included as contributors. 
Duration of the study  
The project duration hinges on reaching the required number of participants, which is 90. 
Technical abbreviations are clearly explained upon first use. Patients participate in the study for 
10 days, during which they receive ultrasound and radionuclide exams, as well as compression 
treatment. The writing style is formal, objective, and free from grammatical, spelling, and 
punctuation errors. Citation and footnote styles follow a consistent format. Physicians examine 
patients before and on day 10 of compression. Patients receive a repeat radionuclide study after 10 
days. 
Anticipated difficulties 
Difficulties with patient recruitment are anticipated due to the fact that gynecologists see and treat 
a majority of female patients with pelvic pain. To mitigate this difficulty, correspondence will be 
sent to women's clinics and outpatient clinics, and communication with gynecological hospitals 
will be established. There is no anticipated funding hurdle, since the study is being conducted as 
a part of the University's scientific work and does not require any extra funding. 
Responsibilities of Researchers  
Sergey Gennadievich Gavrilov, principal investigator 

 
 
Recruiting patients, conducting interviews, performing ultrasound scans, devising treatment plans, 
selecting a treatment method, monitoring compliance with study inclusion requirements, 
documenting procedures, adhering to ethical standards. 
Anatoly Vasilievich Karalkin, researcher.  
Performing radionuclide studies of veins, documentation, statistical analysis.  
Nadezhda Yuryevna Mishakina, researcher.  
Performing ultrasound examinations, preparing documentation, statistical analysis.  
Anastasia Sergeevna Grishenkova, researcher  
Recruitment of patients, repeated examinations of patients, documentation, statistical analysis. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Patient Information  
Title of the study: «Study of venous outflow from the lower limbs in patients with pelvic 
varicosities as a new strategy for compression treatment of pelvic varicose veins and varicose veins 
of the lower limb»  
Organization: Pirogov Russian National Research Medical University 
Introduction 
Before agreeing to participate in this study, it is vital to thoroughly read, comprehend, and 
familiarize yourself with the explanation of all proposed procedures. This document outlines the 
objectives, methodologies, benefits, and potential drawbacks of this study. Furthermore, this 
document details other procedures that may be presented to you and your right to discontinue your 
participation in the study at any point. The study results cannot be guaranteed or assured. 
Scope and purpose of the study 
You are invited to participate in a prospective cohort study to examine the impact of pelvic vein 
dilation on venous outflow from the lower extremities and the impact of compression therapy on 
said venous outflow. This study comprises female patients who have pelvic varicose veins, 
whether or not they exhibit symptoms of chronic vein disease. All consenting patients will receive 
thorough clinical examinations administered by qualified physicians, ultrasound, and radionuclide 
studies for the assessment of venous outflow from their pelvic and lower limb veins. 
Methods of investigation 
Physical examination, duplex ultrasound of pelvic veins and lower limbs, radionuclide 
phlebography of lower limbs, emission computed tomography. Radiation exposure during 
radionuclide studies does not exceed 1.96 mSv. 
Treatment 
Participants in the study found to have lower limb venous outflow disturbance will receive either 
Class 1 or Class 2 compression treatment. Adherence to specific requirements is mandatory, 
including following all procedures as directed and reporting any physical or mental condition 
changes throughout the study. 
Possible risks and inconveniences 
During radionuclide studies, allergic reactions in the form of erythema may occur in extremely 
rare cases. Rare cases of contact dermatitis from a skin reaction to the fabric components of 
compression knitwear have also been reported. 
New data 
Any significant information obtained during the study that may impact your health will be 
provided to you. 
 

 
 
Voluntary participation/ Dropout  
Your participation in this study is voluntary. Refusal to participate will not impact your treatment 
or access to medical care. You may withdraw from the study at any time, and it is essential that 
you inform your doctor immediately. Your doctor may remove you from the study for reasons 
such as non-compliance with instructions, ineligibility, study termination, or administrative 
reasons. 
Expected benefit 
Compression therapy is a safe and effective method for treating CVD. It relieves the 
symptoms of venous insufficiency such as pain, edema, leg heaviness and fatigue. Treatment 
duration depends on disease severity, identified disorders, and planned surgical intervention 
as revealed through ultrasound and radionuclide exams. Compression treatment is usually 
recommended for patients exhibiting clinical symptoms of venous disease such as leg pain, 
edema, and heaviness. However, patients with a combination of pelvic varicosities may have 
disruptions in venous outflow from their lower extremities that do not produce clinical 
symptoms but can cause them. In such instances, patients require compression therapy, which 
does not cause any significant complications or side effects, but improves venous outflow from 
the legs. You will undergo ultrasound and radionuclide studies to determine the extent of 
disturbances in venous outflow from the lower limbs and the impact of pelvic varicosities on the 
functional state of the veins in the lower limbs. Based on conducted studies, identifying factors 
that lead to decreased venous outflow will enable doctors to prescribe compression treatment for 
patients with pelvic varicosities who currently do not experience leg vein problems. However, 
without proper treatment, they may develop them in the future. This study has practical 
significance in improving treatment quality for patients with pelvic varicose veins and preventing 
the development of venous insufficiency in the lower limbs, which can cause edema, pain, and leg 
heaviness. The results hold not only scientific but also practical significance. 
Confidentiality  
All medical records and research materials that can identify you will be kept confidential and will 
not be disclosed in accordance with applicable laws. In the event that the study results are 
published in medical literature, your identity will remain undisclosed. Monitors, auditors, 
representatives of the Ethics Committee, and authorities will have access, subject to 
confidentiality, to the original medical records to verify the accuracy of clinical trial procedures. 
By signing the Informed Consent Form, you consent to this access. If you have any questions 
about your examination and treatment of pelvic varicose veins or require additional information, 
please contact the research staff: Sergei Gennadievich Gavrilov (mobile phone: +7 (916) 
9299947); Karalkin Anatoly Vasilievich (mobile: +7 (915) 9909555); Mishakina Nadezhda 
Yuryevna (mobile: +7 (916) 3480739, Grishenkova Anastasia Sergeevna (mobile: +7 (926) 
1132119). 
 
 
 

 
 
Informed consent form  
Informed consent 
I (full name), __________________________________________________________________ 
informed by the doctor-researcher (full name)_______________________________________ 
about all aspects of the planned clinical trial.  
I received information about the aim and objectives of the clinical trial, information about the 
methods of examination and treatment, the essence of ultrasound, radionuclide studies and 
compression treatment, its positive and negative aspects, the benefits and risks of participating in 
the clinical trial, my rights and responsibilities. I have been warned about possible complications 
and adverse events of ralionuclide testing and compression treatment, and about my actions in 
the event of these complications.  
I had the opportunity to discuss with the research doctor all the questions that interested me and 
was satisfied with the answers I received.  
I am informed that I will be included in the study only after I have undergone a complete 
examination (in accordance with the Protocol) and my medical and physical condition meets the 
conditions for inclusion in this study.  
I voluntarily, knowingly agree to take part in a clinical study devoted to the study of venous 
outflow from the pelvis and lower limbs and the possibilities of compression treatment of 
various disorders of venous outflow from the lower limbs. I am informed that I have the right to 
refuse or at any time to discontinue participation in this study. 
I agree to follow instructions, cooperate in good faith with the study physician, and immediately 
report to him any problems with my health.  
I am advised that if my health is harmed by compression treatment or a medical procedure 
covered by a clinical, ultrasound or radionuclide study plan, I will receive medical treatment that 
will be reimbursed by the insurance company with which I am insured.  
I am informed that information about me and the results of my examination will be confidential 
and can only be disclosed to official representatives while maintaining anonymity.  
By signing the Informed Consent form, I give my permission to access the medical data obtained 
in the study by those responsible for conducting the clinical trial, representatives of the Ethics 
Committee, and official representatives of the Ministry of Health of the Russian Federation. 
I received a signed and dated copy of the Patient Information with a 5-page informed consent 
form.  
Patient's signature  
Full name patient 
Date  
(filled out by the patient)  

 
 
Signature of the research physician  
Full name doctor-researcher  
Date  
(filled out by the research doctor)