Study of the Efficacy and Safety of Longidaze® for the Treatment of Patients With External Genital Endometriosis

Study Overview
=================
Brief Summary
-----------------
A study is being conducted to evaluate the efficacy and safety of Longidaze for the prevention and treatment of external genital endometriosis .

Detailed Description
-----------------
The aim of the study is to compare the outcomes of complex therapy in patients with external genital endometriosis who, in addition to hormonal therapy, were prescribed Longidaze®, vaginal and rectal suppositories, 3000 IU, with the outcomes of therapy in patients who received only hormonal therapy.

Official Title
-----------------
Multicenter Prospective Non-interventional Study of the Efficacy and Safety of Longidaze®, Vaginal and Rectal Suppositories, 3000 IU, for the Treatment of Patients With External Genital Endometriosis

Conditions
-----------------
External Genital Endometriosis

Intervention / Treatment
-----------------
* Drug: Bovhyaluronidase azoximer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented informed consent; Patients over 18 years of age with active menstrual function; Women with external genital endometriosis, confirmed morphologically and visually during laparoscopic or laparotomy surgery performed 10 years to 2 weeks prior to Day 0; Patients in the framework of routine clinical practice in accordance with the instructions for use, prior to inclusion in the study, are assigned one of the following therapy regimens: monotherapy with dienogest 2 mg daily for at least 6 months per os complex treatment with dienogest 2 mg daily for at least 6 months per os in combination with vaginal and rectal suppositories Longidaze® 1 suppository 1 time every 2 days 10 suppositories, and then 1 suppository 1 time in 7 days 17 suppositories for another 120 days; Willingness to use barrier methods of contraception. Exclusion Criteria: Women before menarche or after menopause Adenomyosis; Amenorrhea (more than 3 months in a row within 6 months before screening); Patients who are scheduled to undergo surgery for endometriosis during the study; Hormone therapy for endometriosis or the use of aromatase inhibitors within 16 weeks prior to Day 0; Daily use of pain relievers for 7 consecutive days or more due to any other reason other than endometriosis; 6. Participation in clinical trials less than 30 days before the screening visit and / or 5 drug half-lives, whichever is longer.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Longidaze<br>75 patients receiving combination therapy: Longidaze + dienogest | Drug: Bovhyaluronidase azoximer<br>* Rectally or vaginally 1 suppository of Longidaze every 2 days. The main course of treatment - 10 suppositories (for 30 days). Then (according to the doctor's decision) supportive therapy is prescribed for 1 suppository 1 time in 7 days. Course of supportive treatment - 17 suppositories for another 120 days. The patients took dienogest according to the instructions for use.<br>|
| Control<br>74 patients receiving only Dienogest. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the severity of endometriosis-associated pelvic pain (Day 30) | Changes in the severity of endometriosis-associated pelvic pain by visual analogue scale (VAS) after 30 days from the baseline value in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. The Visual Analogue Scale (VAS) is designed to measure pain intensity. It is a continuous scale in the form of a horizontal line 10 cm (100 mm) long and located on it two extreme points: no pain and the strongest pain you can imagine. The patient is asked to place a line perpendicularly crossing the visual analogue scale at the point that corresponds to his pain intensity. The ruler measures the distance (mm) between no pain and the worst pain imaginable, providing a score range from 0 to 100. A higher score indicates more pain intensity. | Day 0, Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the severity of endometriosis-associated pelvic pain (Days 90, 150, 180) | Changes in the severity of endometriosis-associated pelvic pain according to the VAS after 90, 150 and 180 days relative to the baseline value in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. The Visual Analogue Scale (VAS) is designed to measure pain intensity. It is a continuous scale in the form of a horizontal line 10 cm (100 mm) long and located on it two extreme points: no pain and the strongest pain you can imagine. The patient is asked to place a line perpendicularly crossing the visual analogue scale at the point that corresponds to his pain intensity. The ruler measures the distance (mm) between no pain and the worst pain imaginable, providing a score range from 0 to 100. A higher score indicates more pain intensity. | Day 0, Day 90, Day 150, Day 180 | 
| Change in the Biberoglu and Berman scale | Change in the Biberoglu and Berman scale after 30, 90, 150 and 180 days from the baseline value from the start of treatment in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. The Biberoglu and Berman scale consists of five 4-point scales for assessing the severity of dysmenorrhea, dyspareunia and chronic pelvic pain not associated with menstruation, as well as the assessment of pain and static hyperalgesia during gynecological examination. In each of the scales, 0 points - no symptom, 3 points - the most pronounced symptom. The result is assessed by the sum of points for each symptom. With a sum of points from 1 to 2, pelvic pain is considered mild, from 3 to 5 - moderate, from 6 to 10 - strong, from 11 to 15 - severe. | Day 0, Day 30, Day 90, Day 150, Day 180 | 
| Change in the score on the SF-36 quality of life questionnaire | Change in the score on the SF-36 quality of life questionnaire after 30, 90, 150 and 180 days relative to the baseline value from the start of treatment in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. | Day 0, Day 30, Day 90, Day 150, Day 180 | 
| Change in the severity of uterine bleeding | Change in the severity of uterine bleeding after 30, 90, 150 and 180 days from the start of treatment in patients of the dienogest + Longidaze® combination therapy group compared with patients who received only dienogest. Patients will assess the severity of uterine bleeding in the patient's diary using the Mansfield-Voda-Jorgensen scale. There are five scoring options ranging from light bleeding to heavy bleeding. The rating is determined by the frequency of changing sanitary napkins or tampons, the degree of absorption of these products with blood, and also depends on the absorption properties of these products. | Day 0, Day 30, Day 90, Day 150, Day 180 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
longidaze, external genital endometriosis, bovhyaluronidase azoximer