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出境医 / 临床实验 / Tamoxifen Versus Estradiol for Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Pilot Trial

Tamoxifen Versus Estradiol for Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Pilot Trial

Study Description
Brief Summary:
The purpose of this research study is to evaluate the ability of medicines called tamoxifen or estradiol to prevent annoying vaginal bleeding for arm implant users.

Condition or disease Intervention/treatment Phase
Vaginal Bleeding Drug: Tamoxifen Citrate 10Mg Tab Drug: Estradiol Drug: Placebo Phase 4

Detailed Description:
This pilot study compares the use of tamoxifen to estradiol to placebo for seven days once a month up to 5 months in contraceptive implant users starting from the time of implant initiation. Participants will record bleeding and satisfaction response in a daily text diary.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Tamoxifen Versus Estradiol in the Prevention of Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Controlled Pilot Trial
Estimated Study Start Date : February 2022
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : September 2024
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Tamoxifen
tamoxifen 10mg daily for 7 days
 Drug: Tamoxifen Citrate 10Mg Tab
nonsteroidal antiestrogen for oral administration in 10 mg tablets. Each tablet contains 15.2 mg of tamoxifen citrate which is equivalent to 10 mg of tamoxifen.
Other Name: NOLVADEX
Active Comparator: Estradiol
estradiol 1mg daily for 7 days
 Drug: Estradiol
estradiol tablets for oral administration contains 1 mg of micronized estradiol per tablet.
Other Name: ESTRACE
Placebo Comparator: placebo
placebo daily for 7 days
 Drug: Placebo
A sugar tablet that does not contain any active medicine
Other Name: Inactive drug
Outcome Measures
Primary Outcome Measures :
  1. Duration of bleeding free days [ Time Frame: Up to 28 days ]
    Number of days of no spotting or bleeding after initiation of first treatment until day of subsequent bleeding


Secondary Outcome Measures :
  1. Total number of bleeding free days [ Time Frame: Up to 24 weeks ]
    Total number of no spotting or bleeding days

  2. Days to first re-treatment [ Time Frame: Up to 24 weeks ]
    Number of days between first and second use of medication

  3. Total number of re-treatments [ Time Frame: Up to 24 weeks ]
    Total number of times participant used treatment medication

  4. Satisfaction with bleeding [ Time Frame: Up to 24 weeks ]
    Average satisfaction with bleeding will be assess using daily text surveys. Participants will rate degree of satisfaction with bleeding with the use of symbols (emojis): 1) completely unsatisfied, 2) somewhat unsatisfied, 3) neutral, 4) somewhat satisfied, 5) completely satisfied.

  5. Affects on daily life activities [ Time Frame: Up to 24 weeks ]
    The average affect of bleeding on daily life activities will be assess using daily text surveys. Participants will rate the degree of affects of bleeding on daily life with the use of a visual analogue scale from 0 (no affects) to 100 (highest possible affects)


Eligibility Criteria
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Ages Eligible for Study:   15 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • etonogestrel implant users
  • at time of and/or within 21 days of initial use of etonogestrel implant placement
  • must agree not to take additional hormonal therapy during the study trial period

Exclusion Criteria:

  • within 6 months following vaginal or cesarean delivery
  • within 6 weeks following abortion
  • currently breastfeeding
  • positive pregnancy test
  • contraindications to tamoxifen or estrogen
  • history of thromboembolism
  • undiagnosed abnormal uterine bleeding
  • active cervicitis
  • bleeding disorder
  • use of anticoagulation medications
  • an unwillingness or inability to keep a daily menstrual diary or to follow the study criteria
Contacts and Locations

Contacts
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Contact: Frances E Casey, MD, MPH 8048284409 frances.casey@vcuhealth.org
Contact: Shanthi Ramesh, MD 8043554358 sramesh@vlpp.org

Locations
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United States, Virginia
Shanthi Ramesh
Richmond, Virginia, United States, 23221
Contact: Shanthi Ramesh, MD    804-355-4358    sramesh@vlpp.org   
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Contact: Frances Casey, MD, MPH    804-828-4409    frances.casey@vcuhealth.org   
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
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Principal Investigator: Frances Casey, MD, MPH VCU Health System
Tracking Information
First Submitted Date  ICMJE June 14, 2021
First Posted Date  ICMJE June 21, 2021
Last Update Posted Date December 9, 2021
Estimated Study Start Date  ICMJE February 2022
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2021) 		Duration of bleeding free days [ Time Frame: Up to 28 days ]
Number of days of no spotting or bleeding after initiation of first treatment until day of subsequent bleeding
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2021)
  • Total number of bleeding free days [ Time Frame: Up to 24 weeks ]
    Total number of no spotting or bleeding days
  • Days to first re-treatment [ Time Frame: Up to 24 weeks ]
    Number of days between first and second use of medication
  • Total number of re-treatments [ Time Frame: Up to 24 weeks ]
    Total number of times participant used treatment medication
  • Satisfaction with bleeding [ Time Frame: Up to 24 weeks ]
    Average satisfaction with bleeding will be assess using daily text surveys. Participants will rate degree of satisfaction with bleeding with the use of symbols (emojis): 1) completely unsatisfied, 2) somewhat unsatisfied, 3) neutral, 4) somewhat satisfied, 5) completely satisfied.
  • Affects on daily life activities [ Time Frame: Up to 24 weeks ]
    The average affect of bleeding on daily life activities will be assess using daily text surveys. Participants will rate the degree of affects of bleeding on daily life with the use of a visual analogue scale from 0 (no affects) to 100 (highest possible affects)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tamoxifen Versus Estradiol for Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Pilot Trial
Official Title  ICMJE Tamoxifen Versus Estradiol in the Prevention of Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Controlled Pilot Trial
Brief Summary The purpose of this research study is to evaluate the ability of medicines called tamoxifen or estradiol to prevent annoying vaginal bleeding for arm implant users.
Detailed Description This pilot study compares the use of tamoxifen to estradiol to placebo for seven days once a month up to 5 months in contraceptive implant users starting from the time of implant initiation. Participants will record bleeding and satisfaction response in a daily text diary.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Vaginal Bleeding
Intervention  ICMJE
  • Drug: Tamoxifen Citrate 10Mg Tab
    nonsteroidal antiestrogen for oral administration in 10 mg tablets. Each tablet contains 15.2 mg of tamoxifen citrate which is equivalent to 10 mg of tamoxifen.
    Other Name: NOLVADEX
  • Drug: Estradiol
    estradiol tablets for oral administration contains 1 mg of micronized estradiol per tablet.
    Other Name: ESTRACE
  • Drug: Placebo
    A sugar tablet that does not contain any active medicine
    Other Name: Inactive drug
Study Arms  ICMJE
  • Active Comparator: Tamoxifen
    tamoxifen 10mg daily for 7 days
    Intervention: Drug: Tamoxifen Citrate 10Mg Tab
  • Active Comparator: Estradiol
    estradiol 1mg daily for 7 days
    Intervention: Drug: Estradiol
  • Placebo Comparator: placebo
    placebo daily for 7 days
    Intervention: Drug: Placebo
Publications *
  • Mansour D, Fraser IS, Edelman A, Vieira CS, Kaunitz AM, Korver T, Pong A, Lin J, Shah AK, Fox M, Rekers H, Creinin MD. Can initial vaginal bleeding patterns in etonogestrel implant users predict subsequent bleeding in the first 2 years of use? Contraception. 2019 Oct;100(4):264-268. doi: 10.1016/j.contraception.2019.05.017. Epub 2019 Jun 6.
  • Edelman AB, Kaneshiro B, Simmons KB, Hauschildt JL, Bond K, Boniface ER, Jensen JT. Treatment of Unfavorable Bleeding Patterns in Contraceptive Implant Users: A Randomized Controlled Trial. Obstet Gynecol. 2020 Aug;136(2):323-332. doi: 10.1097/AOG.0000000000003896.
  • Abdel-Aleem H, d'Arcangues C, Vogelsong KM, Gaffield ML, Gülmezoglu AM. Treatment of vaginal bleeding irregularities induced by progestin only contraceptives. Cochrane Database Syst Rev. 2013 Oct 21;(10):CD003449. doi: 10.1002/14651858.CD003449.pub5. Review.
  • Abdel-Aleem H, Shaaban OM, Amin AF, Abdel-Aleem AM. Tamoxifen treatment of bleeding irregularities associated with Norplant use. Contraception. 2005 Dec;72(6):432-7. Epub 2005 Aug 9.
  • DeCensi A, Puntoni M, Guerrieri-Gonzaga A, Caviglia S, Avino F, Cortesi L, Taverniti C, Pacquola MG, Falcini F, Gulisano M, Digennaro M, Cariello A, Cagossi K, Pinotti G, Lazzeroni M, Serrano D, Branchi D, Campora S, Petrera M, Buttiron Webber T, Boni L, Bonanni B. Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. J Clin Oncol. 2019 Jul 1;37(19):1629-1637. doi: 10.1200/JCO.18.01779. Epub 2019 Apr 11.
  • Buzdar AU, Hortobagyi GN, Frye D, Ho D, Booser DJ, Valero V, Holmes FA, Birmingham BK, Bui K, Yeh C, et al. Bioequivalence of 20-mg once-daily tamoxifen relative to 10-mg twice-daily tamoxifen regimens for breast cancer. J Clin Oncol. 1994 Jan;12(1):50-4. Erratum in: J Clin Oncol 1994 Jun;12(6):1337.
  • Macpherson AM, Archer DF, Leslie S, Charnock-Jones DS, Makkink WK, Smith SK. The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium. Hum Reprod. 1999 Dec;14(12):3080-7.
  • Leslie KK, Walter SA, Torkko K, Stephens JK, Thompson C, Singh M. Effect of tamoxifen on endometrial histology, hormone receptors, and cervical cytology: a prospective study with follow-up. Appl Immunohistochem Mol Morphol. 2007 Sep;15(3):284-93.
  • Archer DF, Philput CA, Weber ME. Management of irregular uterine bleeding and spotting associated with Norplant. Hum Reprod. 1996 Oct;11 Suppl 2:24-30.
  • Thomas AM, Hickey M, Fraser IS. Disturbances of endometrial bleeding with hormone replacement therapy. Hum Reprod. 2000 Aug;15 Suppl 3:7-17. Review.
  • Alvarez-Sanchez F, Brache V, Thevenin F, Cochon L, Faundes A. Hormonal treatment for bleeding irregularities in Norplant implant users. Am J Obstet Gynecol. 1996 Mar;174(3):919-22.

*   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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 14, 2021) 		150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • etonogestrel implant users
  • at time of and/or within 21 days of initial use of etonogestrel implant placement
  • must agree not to take additional hormonal therapy during the study trial period

Exclusion Criteria:

  • within 6 months following vaginal or cesarean delivery
  • within 6 weeks following abortion
  • currently breastfeeding
  • positive pregnancy test
  • contraindications to tamoxifen or estrogen
  • history of thromboembolism
  • undiagnosed abnormal uterine bleeding
  • active cervicitis
  • bleeding disorder
  • use of anticoagulation medications
  • an unwillingness or inability to keep a daily menstrual diary or to follow the study criteria
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Female
Ages  ICMJE 15 Years to 45 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Frances E Casey, MD, MPH 8048284409 frances.casey@vcuhealth.org
Contact: Shanthi Ramesh, MD 8043554358 sramesh@vlpp.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04933240
Other Study ID Numbers  ICMJE HM20021901
Has Data Monitoring Committee Not Provided
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.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Frances Casey, MD, MPH VCU Health System
PRS Account Virginia Commonwealth University
Verification Date December 2021

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