Comparison Between the Effects of Implantable Gestrinone and Oral Dienogest in the Treatment of Endometriosis

Comparison Between the Effects of Implantable Gestrinone and Oral Dienogest in the Treatment of Endometriosis: Randomized Controlled Clinical Trial

This study aims to evaluate the effects of therapy with implantable Gestrinone compared to oral Dienogest in relieving complaints related to endometriosis.

Study Overview

• Status: Recruiting
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Implantable gestrinone; Drug: Oral Dienogest

Detailed Description

Patient recruitment will be carried out on a prospective basis and based on the group of patients from the private Medical Clinics in 4 cities (Campina Grande - Pb, São Paulo - SP, São José dos Campos - SP and Brasilia-DF). The study will include 70 adult female patients of menstrual age, pre-menopause (18 to 45 years old), who seek medical treatment to alleviate complaints related to endometriosis. The selected patients will be randomly allocated into two groups, in a 1:1 ratio. Control Group (n=35) - treatment with oral Dienogest - and Test Group (n=35) - Implantation of Gestrinone pellets. Follow-up visits will be scheduled after 1 week and 1, 3, 6, 9 and 12 months of initiation of therapy. Therapies will be compared with respect to the effects on the severity of dysmenorrhea, dyspareunia and non-cyclical pelvic pain (Verbal Scale and Visual Analogue Scale), level of Uterine Bleeding assessed by PBAC, systemic effects (hormonal, hepatic, lipid profile, cell concentration red, clotting factor - assessed through blood tests), endometriosis lesions, endometrial thickness (transvaginal ultrasound), body composition (bioimpendance test), quality of life (EHP30) and sexual function (female sexual function index ) - FSFI. Data analysis will be carried out using validated statistical software. Chi-square or Fisher's exact tests will be used to compare qualitative variables, while independent t-tests will be used to compare quantitative variables between the two groups. Analysis of variance with repeated measures will be used to compare the average pain intensity over time. The significance level for all tests will be p<0.05.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: André V. A. Florentino, Dr; Phone Number: +55 83 982001868; Email: f.andrevinicius@gmail.com

Study Locations

• Brazil
  • São Paulo, Brazil, 05.688-021
    • Recruiting
    • Dra Juliana Bicca Endocrinologia e Medicina Funcional LTDA
    • Contact: Juliana B. Nascimento, Dr; Phone Number: +55 11 3027-1500; Email: drajubicca@gmail.com
    • Principal Investigator: Juliana B. Nascimento, Dr
  • Distrito Federal
    • Brasília, Distrito Federal, Brazil, 70.390-150
      • Recruiting
      • Gm Ignacio Atividade Medica LTDA
      • Contact: Giovanna M. Ignácio, Dr; Phone Number: +55 61 99266-1706; Email: dragiovannamilhomem@gmail.com
      • Principal Investigator: Giovanna M. Ignácio, Dr
  • Paraíba
    • Campina Grande, Paraíba, Brazil, 58.400-506
      • Recruiting
      • Instituto Longevite Servicos Medicos LTDA
      • Contact: André V.A. Florentino, Dr; Phone Number: +55 83 3077-8928; Email: f.andrevinicius@gmail.com
      • Principal Investigator: f.andrevinicius@gmail.com V.A. Florentino, Dr
  • São Paulo
    • São José dos Campos, São Paulo, Brazil, 12.246-876
      • Recruiting
      • Jpml Clinica Medica LTDA
      • Contact: Juliana P.M. Lima, Dr; Phone Number: +55 12 3939-6436; Email: drajulianapaola@gmail.com
      • Principal Investigator: Juliana P.M. Lima, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult female patients of menstrual age, pre-menopause (18 to 45 years old), who seek medical treatment to alleviate complaints related to endometriosis, who are not undergoing other therapies to treat them.
• Patients must have a diagnosis of Grade 1 or 2 endometriosis assessed by imaging tests (ultrasound with bowel preparation and/or MRI of the pelvis with bowel preparation)14, have a BMI of up to 25kg/m2, and weigh between 50 and 70kg.

Exclusion Criteria:

• Pregnant patients (supporting test must be presented)
• Breastfeeding women, using other hormonal contraceptive methods or copper or silver IUDs, who have polycystic ovaries, and/or hyperandrogenism.
• Patients using medications that may interfere with androgen metabolism within 4 weeks of screening or during the study.
• Patients with a history of liver disease, cardiovascular disease (myocardial infarction, unstable angina or heart failure), active hepatitis, liver neoplasia or renal failure
• Patient who are scheduled for surgical treatment during the study period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Implantable Gestrinone; Implantation of Gestrinone pellets - Eligible patients will undergo implantation of Gestrinone pellets (bio meds Brasil, Florianópolis, Brazil) subcutaneously, in the gluteal region, using aseptic technique under local anesthesia. Patients will use 1.6mg/kg of weight to treat endometriosis. A second implantation procedure will be performed 6 months after the first, allowing evaluation of the effects of the therapy over a period of 12 months.	Drug: Implantable gestrinone; 1.6mg/kg of weight of gestrinone in pellets (bio meds Brasil, Florianópolis, Brazil) subcutaneously, in the gluteal region.; Other Names: Gestrinone pellet
Active Comparator: Oral Dienogest; Patients will receive the medication to be administered orally at 2mg daily for 12 months.	Drug: Oral Dienogest; Administered orally at 2 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of dysmenorrhea severity	Patients will be instructed to rate the intensity of dysmenorrhea at each visit after the first month of treatment, using a modified verbal scale from 0 to 3, as suggested by Biberoglu and Behrman. Patients should also rate the intensity of the symptoms using a 100 mm visual analogue scale.	Pre-treatment, 1 week, 1, 3 , 6 and 12 months
Evaluation of dyspareunia severity	Patients will be instructed to rate the intensity of deep dyspareunia at each visit after the first month of treatment, using a modified verbal scale from 0 to 3, as suggested by Biberoglu and Behrman. Patients should also rate the intensity of the symptoms using a 100 mm visual analogue scale.	Pre-treatment, 1 week, 1, 3 , 6 and 12 months
Evaluation of non-cyclical pelvic pain severity	Patients will be instructed to rate the intensity of pelvic pain (outside the menstrual period), at each visit after the first month of treatment, using a modified verbal scale from 0 to 3, as suggested by Biberoglu and Behrman. Patients should also rate the intensity of the symptoms using a 100 mm visual analogue scale.	Pre-treatment, 1 week, 1, 3 , 6 and 12 months
Evaluation of endometriosis foci regression	Assessment of endometriosis lesions and endometrial thickness on Transvaginal Ultrasound with bowel preparation and/or MRI of the pelvis with bowel preparation - All patients will be referred, at pre-treatment and at 6 and 12 month visits, to undergo transvaginal ultrasound to assess the presence or absence of endometriotic lesions, in addition to controlling the thickness of the endometrium.	Pre-treatment, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of quality of life	The evaluation of the influence of complaints on the impact of endometriosis on patients' quality of life will be carried out using the EHP-30 questionnaires validated for the Portuguese language.	Pre-treatment, 6 and 12 months
Evaluation of adverse effect	Evaluation of sings and symptoms. In addition, it will be evaluated at each visit the serum levels of Estradiol, Sex Hormone Binding Globulin (SHBG), Progesterone, Total and free Testosterone, FSH, LH, Hepatic transaminase (TGO, TGP, GGT), Total cholesterol and fractions, Triglycerides, Red cell concentration, Coagulation factors , Homocysteine, Fibrinogen, DHT.	Pre-treatment, 1 week, 1, 3 , 6 and 12 months
Evaluation of abnormal Uterine Bleeding (AUB)	The duration and intensity of menstrual flow will be recorded pre-treatment and at each visit after the first month of treatment. Abnormal uterine bleeding will be defined as a PBAC (Pictorial blood loss assessment chart) score greater than 100.	Pre-treatment, 1, 3 , 6 and 12 months
Evaluation of sexual function	The assessment of sexual function (desire, excitement, lubrication, orgasm, satisfaction and pain) will be carried out through the application of the Female Sexual Function Index.	Pre-treatment, 1 week, 1, 3 , 6 and 12 months
Evaluation of body composition	Body composition will be assessed using the tetrapolar Bioimpedance test with the Indoby device (weight, percentage of lean mass and fat mass)	Pre-treatment, 3 , 6 and 12 months

Collaborators and Investigators

• Sponsor: Bio Meds Pharmaceutica Ltda

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: August 4, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 4, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Endometriosis; Dienogest; Implantable Gestrinone
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Progestins; Contraceptive Agents, Male; Dienogest; Gestrinone
• Other Study ID Numbers: CS.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The patients data will be reported together in the final report.

Drug and device information, study documents

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