Levonorgestrel-releasing Intrauterine System in Patients With Endometriosis

Study Overview
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Brief Summary
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The hemostatic and inflammatory systems may activate each other. Endometriosis is a chronic inflammatory disease affecting 10% of women. The objective of this study is to compare the hemostatic effects of two treatments widely prescribed to women with endometriosis: the levonorgestrel intrauterine system (LNG-IUS) and the gonadotropin-releasing hormone analog (GnRHa) leuprolide acetate. Hypothesis: H0: There is no alteration in hemostatic system with the use of GnRHa or LNG-IUS H1: There is alteration in hemostatic system with the use of GnRHa or LNG-IUS

Detailed Description
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Materials and Methods: In this randomized open-label controlled trial, 44 women with endometriosis will be randomly allocated to one of two groups: 22 women will be assigned to use LNG-IUS and 22 to use GnRHa. The assessed variables will be D-dimers, fibrinogen, prothrombin time, activated partial thromboplastin time, coagulation factors (F) II, V, VII, VIII, IX, X, and XI, antithrombin (AT), protein C, free protein S, tissue plasminogen activator (t-PA), α2-antiplasmin, thrombin-antithrombin complex, and prothrombin fragment 1+2. All variables will be assessed before treatment and six months after treatment onset.

Official Title
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Effects of the Levonorgestrel-releasing Intrauterine System Compared With the Leuprolide Acetate in Patients With Endometriosis: a Randomized Trial

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: LNG-IUS: levonorgestrel intrauterine system
* Drug: GnRHa: leuprolide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: to have endometriosis aged 18 to 40 years Being without contraceptives for at least 3 months or with depot medroxyprogesterone acetate or GnRHa for at least 6 months at the time of randomization. Exclusion Criteria: obese patients with a body mass index (BMI) ≥30 kg/m2 smokers diabetics alcohol or drug users patients currently wishing to conceive patients with chronic diseases (except endometriosis) patients with infectious processes patients with a personal and/or family history of thromboembolic events patients taking medications known to interfere with inflammation markers (such as hormonal and nonhormonal anti-inflammatory agents) within the 15 days before the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LNG-IUS<br>LNG-IUS: levonorgestrel intrauterine system | Drug: LNG-IUS: levonorgestrel intrauterine system<br>* LNG-IUS (levonorgestrel intrauterine system) is inserted until the fifth day of the cycle. It releases 20 mcg/day of LNG<br>* Other names: Mirena;|
| Active Comparator: GnRHa<br>GnRHa: leuprolide | Drug: GnRHa: leuprolide<br>* 3.75 mg leuprolide injected intramuscularly on a monthly basis<br>* Other names: Lupron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in d-dimer | to compare the change over 6 months (6 months - baseline) on d-dimer of two treatments widely prescribed to women with endometriosis, LNG-IUS and GnRHa leuprolide acetate. | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in Coagulation times | To compare the change over 6 months (6 months - baseline) of coagulation times as a composite measure of 3 variables: Thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) | baseline and 6 months | 
| change from baseline in procoagulatory variables | to compare the change over 6 months (6 months - baseline) on procoagulatory variables (Fibrinogen, coagulation factors II, V, VII, VIII, IX, X, and XI) of two treatments widely prescribed to women with endometriosis, LNG-IUS and GnRHa leuprolide acetate. | baseline and 6 months | 
| Change from baseline in natural anticoagulants | to compare the change over 6 months (6 months - baseline) on natural anticoagulants (Protein C and antithrombin) of two treatments widely prescribed to women with endometriosis, LNG-IUS and GnRHa leuprolide acetate. | baseline and 6 months | 
| Change in activation of the coagulation cascade markers | to compare the change over 6 months (6 months - baseline) on activation of the coagulation cascade markers (concentrations of the thrombin-antithrombin complex and prothrombin fragment 1+2) of two treatments widely prescribed to women with endometriosis, LNG-IUS and GnRHa leuprolide acetate. | baseline and 6 months | 
| Change from baseline on antifibrinolytic variables | to compare the change over 6 months (6 months - baseline) on antifibrinolytic variables (Plasminogen activator inhibitor 1, α-2 antiplasmin) of two treatments widely prescribed to women with endometriosis, LNG-IUS and GnRHa leuprolide acetate. | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometriosis, blood coagulation, levonorgestrel, GnRH agonist, progesterone-releasing intrauterine device