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Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis (APPOSE)

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ClinicalTrials.gov Identifier: NCT04002141
Recruitment Status : Recruiting
First Posted : June 28, 2019
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE May 28, 2019
First Posted Date  ICMJE June 28, 2019
Last Update Posted Date August 11, 2020
Actual Study Start Date  ICMJE September 17, 2019
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2019)
Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). ]
To evaluate how letrozole impacts pain scores throughout controlled ovarian hyperstimulation in patients with endometriosis. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot pain score will be compared between patients with endometriosis receiving placebo and with endometriosis receiving letrozole.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2020)
  • Average Delta in Endometriosis Pain Score Pre and Post Stimulation Compared to No Endometriosis [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). ]
    To evaluate the impact of endometriosis on pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot will be compared between patients with endometriosis receiving placebo and patients without endometriosis.
  • Trend in Endometriosis Pain Score Pre and Post Stimulation With Use Of Letrozole [ Time Frame: Pre-stimulation through 12 weeks post retrieval ]
    To evaluate the impact of letrozole on endometriosis pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The trend in pain scores from pre-stimulation through 12 weeks post retrieval will be compared between patients with endometriosis receiving placebo, patients with endometriosis receiving letrozole and patients without endometriosis.
  • Does Letrozole Impact Embryo and Egg Quantity in Endometriosis [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). ]
    To describe the impact of letrozole on egg/embryo quality in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation. The number of eggs retrieved per AFC and the number of eggs retrieved per total number of mature follicles will be compared between the two groups.
  • Follicular Fluid [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). ]
    To compare follicular fluid average estradiol levels between placebo, letrozole and control groups.
  • Pregnancy Outcomes [ Time Frame: Up to 2 years. ]
    To compare pregnancy rates in the placebo, letrozole and control groups. Pregnancy will be defined as positive serum hCG after transfer of embryo. The rate will determined by positive hCG per transfer.
  • Egg Maturity [ Time Frame: Baseline ultrasound to time of cryopreservation of eggs/embryos, which occurs within 7 days of retrieval.. ]
    To describe the impact of letrozole on egg maturity. Measured by number of MII eggs per total number eggs retrieved in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation.
  • Embryo Grade [ Time Frame: 2 weeks ]
    To describe the impact of letrozole on embryo quality. Measured by fraction of freezable quality embryos (6c or greater, grades 1-2 for symmetry and fragmentation) in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2019)
  • Average Delta in Endometriosis Pain Score Pre and Post Stimulation Compared to No Endometriosis [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). ]
    To evaluate the impact of endometriosis on pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot will be compared between patients with endometriosis receiving placebo and patients without endometriosis.
  • Trend in Endometriosis Pain Score Pre and Post Stimulation With Use Of Letrozole [ Time Frame: Pre-stimulation through 12 weeks post retrieval ]
    To evaluate the impact of letrozole on endometriosis pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The trend in pain scores from pre-stimulation through 12 weeks post retrieval will be compared between patients with endometriosis receiving placebo, patients with endometriosis receiving letrozole and patients without endometriosis.
  • Does Letrozole Impact Embryo and Egg Quantity in Endometriosis [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). ]
    To describe the impact of letrozole on egg/embryo quality in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation. The number of eggs retrieved per AFC and the number of eggs retrieved per total number of mature follicles will be compared between the two groups.
  • Follicular Fluid [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). ]
    To compare follicular fluid average estradiol levels between placebo, letrozole and control groups.
  • Pregnancy Outcomes [ Time Frame: Up to 2 years. ]
    To compare pregnancy rates in the placebo, letrozole and control groups. Pregnancy will be defined as positive serum hCG after transfer of embryo. The rate will determined by positive hCG per transfer.
  • Egg Maturity [ Time Frame: Baseline ultrasound to time of cryopreservation of eggs/embryos, which occurs witihin 7 days of retrieval.. ]
    To describe the impact of letrozole on egg maturity. Measured by number of MII eggs per total number eggs retrieved in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation.
  • Embryo Grade [ Time Frame: 2 weeks ]
    To describe the impact of letrozole on embryo quality. Measured by fraction of freezable quality embryos (6c or greater, grades 1-2 for symmetry and fragmentation) in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis
Official Title  ICMJE Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis
Brief Summary Randomized double blinded placebo-controlled trial to evaluate the impact of ovarian hyperstimulation on endometriosis-related symptoms and to evaluate the impact of letrozole use during ovarian hyperstimulation with respect to endometriosis-related symptoms, embryo/egg quality and quantity, and pregnancy rates.
Detailed Description

Randomized double blinded placebo-controlled trial to evaluate: (1) the impact of letrozole use during ovarian hyperstimulation with respect to endometriosis-related symptoms, embryo/egg quality and quantity, and pregnancy rates, (2) the impact of ovarian hyperstimulation on endometriosis-related symptoms.

There will be a total of 60 participants, 20 participants with endometriosis randomized to the placebo group, 20 participants with endometriosis randomized to the letrozole group and 20 control patients with no history of endometriosis. Letrozole and placebo medication will be started on the first day of gonadotropin injections and continued until the day of trigger shot. Medication will be restarted the night of egg retrieval and continued for 2 weeks post retrieval. Endometriosis associated symptoms will be evaluated using a survey modeled after the clinical survey developed by the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project. Surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE
  • Endometriosis
  • Ovarian Hyperstimulation
Intervention  ICMJE
  • Drug: Placebo oral tablet
    1 tablet oral daily
  • Drug: Letrozole
    5mg oral daily
Study Arms  ICMJE
  • Experimental: Endometriosis Letrozole
    Participants will be asked to take 5mg letrozole daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to letrozole. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.
    Intervention: Drug: Letrozole
  • Placebo Comparator: Endometriosis Placebo
    Participants will be asked to take one tablet placebo daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to placebo. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.
    Intervention: Drug: Placebo oral tablet
  • No Intervention: No Endometriosis Control
    Participants will be asked to complete surveys during their ovarian stimulation and up to 12 weeks following retrieval to evaluate symptoms of pelvic pain. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2022
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18-42 years
  • Planning to undergo controlled ovarian hyperstimulation
  • Prior diagnosis of endometriosis by one of the following: (1) surgical diagnosis (2) endometrioma on pelvic ultrasound
  • Planning to freeze all retrieved oocytes/embryos prior to transfer

Exclusion Criteria:

  • Hypersensitivity to letrozole
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 42 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Kaitlyn A Wald, MD 415-353-7475 Kaitlyn.Wald@ucsf.edu
Contact: Marcelle I Cedars, MD 415-353-7475
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04002141
Other Study ID Numbers  ICMJE 18-26544
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marcelle I Cedars University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP