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

NCT04933240 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: HM20021901
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Vaginal Bleeding

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Total number of bleeding free days

  Up to 24 weeks

• Days to first re-treatment

  Up to 24 weeks

• Total number of re-treatments

  Up to 24 weeks

• Satisfaction with bleeding

  Up to 24 weeks

• Affects on daily life activities

  Up to 24 weeks

Study Arms (3)

Tamoxifen

ACTIVE COMPARATOR

tamoxifen 10mg daily for 7 days

Drug: Tamoxifen Citrate 10Mg Tab

Estradiol

ACTIVE COMPARATOR

estradiol 1mg daily for 7 days

Drug: Estradiol

placebo

PLACEBO COMPARATOR

placebo daily for 7 days

Drug: Placebo

Interventions

Tamoxifen Citrate 10Mg Tab DRUG

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.

Also known as: NOLVADEX

Tamoxifen

Estradiol DRUG

estradiol tablets for oral administration contains 1 mg of micronized estradiol per tablet.

Also known as: ESTRACE

Estradiol

Placebo DRUG

A sugar tablet that does not contain any active medicine

Also known as: Inactive drug

placebo

Eligibility Criteria

• Age: 15 Years - 45 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (2)

Shanthi Ramesh

Richmond, Virginia, 23221, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (11)

• 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.

  PMID: 31176688 BACKGROUND

• 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.

  PMID: 32649493 BACKGROUND

• Abdel-Aleem H, d'Arcangues C, Vogelsong KM, Gaffield ML, Gulmezoglu AM. Treatment of vaginal bleeding irregularities induced by progestin only contraceptives. Cochrane Database Syst Rev. 2013 Oct 21;2013(10):CD003449. doi: 10.1002/14651858.CD003449.pub5.

  PMID: 24146298 BACKGROUND

• 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. doi: 10.1016/j.contraception.2005.05.015. Epub 2005 Aug 9.

  PMID: 16307966 BACKGROUND

• 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.

  PMID: 30973790 BACKGROUND

• 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. doi: 10.1200/JCO.1994.12.1.50.

  PMID: 8270984 BACKGROUND

• 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. doi: 10.1093/humrep/14.12.3080.

  PMID: 10601100 BACKGROUND

• 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. doi: 10.1097/01.pai.0000213147.54901.12.

  PMID: 17721273 BACKGROUND

• 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. doi: 10.1093/humrep/11.suppl_2.24.

  PMID: 8982742 BACKGROUND

• Thomas AM, Hickey M, Fraser IS. Disturbances of endometrial bleeding with hormone replacement therapy. Hum Reprod. 2000 Aug;15 Suppl 3:7-17. doi: 10.1093/humrep/15.suppl_3.7.

  PMID: 11041216 BACKGROUND

• 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. doi: 10.1016/s0002-9378(96)70326-5.

  PMID: 8633669 BACKGROUND

MeSH Terms

Conditions

Uterine Hemorrhage

Interventions

Tamoxifen; Estradiol

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Frances Casey, MD, MPH

  VCU Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 21, 2021
• Study Start: May 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 3, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)