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Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis (PREGnant)

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ClinicalTrials.gov Identifier: NCT04173169
Recruitment Status : Not yet recruiting
First Posted : November 21, 2019
Last Update Posted : May 22, 2020
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Colorado, Denver
Northwestern University
University of North Carolina
Information provided by (Responsible Party):
Yale University

Brief Summary:
A Phase 3 randomized clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to placebo.

Condition or disease Intervention/treatment Phase
Infertility Endometriosis Drug: Elagolix 200 MG Drug: Placebo Phase 3

Detailed Description:
Infertility is a common complication of endometriosis; while IVF successfully treats endometriosis-associated infertility, pregnancy rates are diminished compared to other etiologies of infertility. The study's long- term objectives are to better identify and treat endometriosis related infertility. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to placebo. The use of gonadotropin releasing hormone (GnRH) agonist prior to IVF has been suggested to improve success, however studies have been small and rarely reported live birth rates. Further, use of this approach is limited by the long treatment time required. Recent approval of an oral GnRH antagonist for endometriosis provides a novel option for women with endometriosis who are undergoing IVF. This agent avoids parenteral administration and the prolonged delay in initiation of action as was seen with GnRH agonists. There have been no studies on the efficacy of GnRH antagonists for the treatment of endometriosis-related infertility. The investigators propose a randomized clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators have also recently demonstrated aberrant microRNAs in the circulation of women with endometriosis, a panel of which investigators have subsequently validated as a biomarker with high sensitivity and specificity for the detection of active disease. It is secondarily proposed that disease biomarkers will identify women who will benefit from GnRH antagonist pre-treatment, allowing a precision medicine approach to endometriosis-related infertility. The proposed study is significant due to the common occurrence of both infertility and endometrioses as well as the lack of precision in both diagnosis and therapy. The investigators use an innovative approach to identify endometriosis as well as a novel intervention designed to improve the prognosis of women with endometriosis undergoing IVF.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 814 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Half of the subjects (407) will receive elagolix 200mg twice a day (BID) and the other half of subjects (407) will receive placebo BID, both for a minimum of 60 days before IVF cycle start. For convenience of IVF cycle scheduling, participants may receive up to an additional 14 days of intervention (elagolix or placebo) beyond the minimum 60 days of pre-IVF treatment, such that the last dose of study intervention (elagolix or placebo)is received no more than 24 hours before start of IVF treatment protocol.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: A computer-generated randomization list will be created by the PREGnant Data Coordinating Center (DCC) and randomization will be performed prior to the first dose of elagolix. Randomization will have random sizes (2, 4, or 6) of blocks and be stratified by site, i.e. whole blocks are assigned to sites. The randomization list will not be available to any person involved in the conduct and evaluation of the trial until the trial is complete and database is declared clean and is released by the DCC. Likewise, treatment allocation information will not be accessible to investigators (except for serious safety concerns), trial staff at the site or central laboratory personnel during the trial.
Primary Purpose: Treatment
Official Title: Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis - A Prospective Double-blind Placebo-controlled Trial
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis

Arm Intervention/treatment
Experimental: Pre-IVF Treatment with 60 day course of oral GnRH antagonist
Subjects will be randomized to elagolix 200mg BID. The medication will be taken orally and subjects will be counseled to take the medication at the same time each day.
Drug: Elagolix 200 MG
Elagolix tablet
Other Name: Orlissa

Placebo Comparator: Pre-IVF Treatment with 60 day course of Placebo
Subjects will be randomized to placebo, BID. The medication will be taken orally and subjects will be counseled to take the medication at the same time each day.
Drug: Placebo
Sugar pill manufactured to mimic Elagolix 200mg




Primary Outcome Measures :
  1. Live birth rate [ Time Frame: Up to 15 months ]
    Live birth rate per participant is defined as live birth at ≥24 weeks of gestation.


Secondary Outcome Measures :
  1. Live birth rate per transfer [ Time Frame: Up to 15 months ]
    Live birth rate per participant per ET cycle is defined as live birth at ≥24 weeks of gestation. (parity per transfer)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 38 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women who plan to undergo IVF for treatment of infertility.
  2. Age ≥18 and <38 years at time of signing informed consent.
  3. Documentation of diagnosis of endometriosis by surgical visualization of endometriosis (laparoscopy or laparotomy) or diagnosis by pathology within the last 10 years before the initial trial entry visit or documentation of ovarian endometrioma >2 cm or two or more smaller endometriomas that total >2 cm in diameter. If entry is based on the presence of an endometrioma, transvaginal ultrasound evaluation must document the same unambiguous endometrioma on two separate occasions in more than one menstrual cycle. Images will be printed or transmitted electronically and read centrally by investigators at Yale to assure uniform diagnostic criteria (classic ground glass appearance) are applied.
  4. Body mass index (BMI) of 18-40 kg/m2 (both inclusive) at screening.
  5. AMH > 0.8 ng/ml, resulted within 6 months of planned IVF cycle start.
  6. Uterine cavity assessment by sonohysterogram or hysteroscopy within 6 months indicating absence of focal intracavitary pathology and hence adequacy for embryo transfer. Ultrasound features suggestive of adenomyosis will be acceptable for inclusion. Type 3 fibroids are allowed up to 4cm size
  7. Presence of at least one ovary with no clinically significant abnormalities other than endometrioma. For eligible subjects with evidence of a hemorrhagic ovarian cyst, a repeat US will be needed in a subsequent menstrual cycle to ensure persistent cyst for patient to be deemed eligible.
  8. Negative urine or cervical swab for gonorrhea and chlamydia within 12 months of screening.
  9. Willing and able to comply with trial procedures, including reporting of obstetrical outcomes after delivery.

Exclusion Criteria:

  1. Use of GnRH agonists or antagonists within 6 months of study start, unless the antagonist was a part of a regular IVF cycle.
  2. Use of depot medroxyprogesterone acetate (MPA) or birth control implants (e.g. Implanon® or Nexplanon®) within 10 months of study start.
  3. Continuous use of oral progestins (MPA, NETA) within 3 months of study start.
  4. Use of aromatase inhibitors, danazol or hormonal contraceptives (Including combined oral contraceptive pill, progestin-only pill, transdermal patch or contraceptive ring) within 1 month of study start.
  5. Pregnancy greater than 8 weeks in length within the last 6 months.
  6. Number of previous IVF/ICSI attempts ≥3
  7. Presence of hydrosalpinx measuring >2cm on ultrasound, untreated endometrial polyps or intrauterine adhesions.
  8. Abnormal cytology on a pap smear within last year. (CIN1 or HPV okay, CIN2 excluded unless treated and cleared, CIN3 excluded).
  9. History of malignancy within 5 years of the start of screening, except for treated basal cell carcinoma and squamous cell carcinoma of the skin.
  10. Any suicide attempts in last 1 year.
  11. Hypersensitivity to the study drugs.
  12. Planned surgical treatment of endometriosis or planned surgery in the abdominal-pelvic area within the duration of the trial.
  13. Untreated abnormal prolactin or TSH
  14. Any conditions that preclude pregnancy. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04173169


Contacts
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Contact: Heping Zhang, PhD 203-785-5185 adriana.zuniga@yale.edu
Contact: Adriana Zuniga 203-785-5185 adriana.zuniga@yale.edu

Sponsors and Collaborators
Yale University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Colorado, Denver
Northwestern University
University of North Carolina
Investigators
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Study Director: Esther Eisenberg, MD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Hugh Taylor, MD Yale University
Study Director: Heping Zhang, PhD Yale University
Study Director: Nanette Santoro, MD University of Colorado, Denver
Study Director: Jared Robbins, MD Northwestern University
Study Director: Steven Young, MD, PhD University of North Carolina
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT04173169    
Other Study ID Numbers: 2000027121
1R01HD100336-01 ( U.S. NIH Grant/Contract )
First Posted: November 21, 2019    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infertility
Endometriosis
Genital Diseases, Male
Genital Diseases, Female