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

Vaginal Bleeding Clinical Trial

Official title:

Tamoxifen Versus Estradiol in the Prevention of Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Controlled Pilot Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04933240
• Other study ID #: HM20021901
• Status: Withdrawn
• Phase: Phase 4
• Start date: May 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2022
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Uterine Hemorrhage
• Vaginal Bleeding

Intervention

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.
• Estradiol
estradiol tablets for oral administration contains 1 mg of micronized estradiol per tablet.
• Placebo
A sugar tablet that does not contain any active medicine

Locations

Country	Name	City	State
United States	Shanthi Ramesh	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Thomas AM, Hickey M, Fraser IS. Disturbances of endometrial bleeding with hormone replacement therapy. Hum Reprod. 2000 Aug;15 Suppl 3:7-17. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of bleeding free days	Number of days of no spotting or bleeding after initiation of first treatment until day of subsequent bleeding	Up to 28 days
Secondary	Total number of bleeding free days	Total number of no spotting or bleeding days	Up to 24 weeks
Secondary	Days to first re-treatment	Number of days between first and second use of medication	Up to 24 weeks
Secondary	Total number of re-treatments	Total number of times participant used treatment medication	Up to 24 weeks
Secondary	Satisfaction with bleeding	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.	Up to 24 weeks
Secondary	Affects on daily life activities	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)	Up to 24 weeks