Levonorgestrel-releasing Intrauterine System in Patients With Endometriosis (SIU-LNG)

• ClinicalTrials.gov Identifier: NCT02158845
• Recruitment Status: Completed
• First Posted: June 9, 2014
• Last Update Posted: January 21, 2015
• Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo; Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Information provided by (Responsible Party): Carolina Sales Vieira, University of Sao Paulo

Tracking Information

• First Submitted Date: May 31, 2014
• First Posted Date: June 9, 2014
• Last Update Posted Date: January 21, 2015
• Study Start Date: February 2010
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2014)

change from baseline in d-dimer [ Time Frame: baseline and 6 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 5, 2014)

• change from baseline in Coagulation times [ Time Frame: baseline and 6 months ]
  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)
• change from baseline in procoagulatory variables [ Time Frame: baseline and 6 months ]
  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.
• Change from baseline in natural anticoagulants [ Time Frame: baseline and 6 months ]
  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.
• Change in activation of the coagulation cascade markers [ Time Frame: baseline and 6 months ]
  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.
• Change from baseline on antifibrinolytic variables [ Time Frame: Baseline and 6 months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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: 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label)
• Condition: Endometriosis

Intervention

• Drug: LNG-IUS: levonorgestrel intrauterine system
  LNG-IUS (levonorgestrel intrauterine system) is inserted until the fifth day of the cycle. It releases 20 mcg/day of LNG
  Other Name: Mirena
• Drug: GnRHa: leuprolide
  3.75 mg leuprolide injected intramuscularly on a monthly basis
  Other Name: Lupron

Study Arms

• Active Comparator: LNG-IUS
  LNG-IUS: levonorgestrel intrauterine system
  Intervention: Drug: LNG-IUS: levonorgestrel intrauterine system
• Active Comparator: GnRHa
  GnRHa: leuprolide
  Intervention: Drug: GnRHa: leuprolide

• Publications *: Yamaguti EM, Brito MB, Ferriani RA, Garcia AA, Rosa-e-Silva JC, Vieira CS. Comparison of the hemostatic effects of a levonorgestrel-releasing intrauterine system and leuprolide acetate in women with endometriosis: a randomized clinical trial. Thromb Res. 2014 Dec;134(6):1193-7. doi: 10.1016/j.thromres.2014.09.014. Epub 2014 Sep 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 5, 2014): 44
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT02158845
• Other Study ID Numbers: SIU-LNG 001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Carolina Sales Vieira, University of Sao Paulo
• Study Sponsor: University of Sao Paulo

Collaborators

• Fundação de Amparo à Pesquisa do Estado de São Paulo
• Conselho Nacional de Desenvolvimento Científico e Tecnológico

Investigators

• Principal Investigator: CAROLINA S VIEIRA, MD, PhD; Sao Paulo University

• PRS Account: University of Sao Paulo
• Verification Date: January 2015