Vaginal BleedingPhase 4NCT04933240
Tamoxifen Versus Estradiol for Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Pilot Trial
A Phase 4 study testing Tamoxifen Citrate 10Mg Tab and Estradiol in people with Vaginal Bleeding, run by Virginia Commonwealth University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 15 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Vaginal Bleeding
- What is being tested?
- Tamoxifen Citrate 10Mg Tab and Estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2022to Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 45 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Shanthi Ramesh
Richmond, Virginia, 23221
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Tamoxifen Versus Estradiol in the Prevention of Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Controlled Pilot Trial
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.
Read the 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.
- Conditions
- Vaginal Bleeding
- Being tested
- Tamoxifen Citrate 10Mg Tab, Estradiol, Placebo
- Medical subject headings
- Uterine Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tamoxifen Citrate 10Mg TabDrug
Also called NOLVADEX
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.
EstradiolDrug
Also called ESTRACE
estradiol tablets for oral administration contains 1 mg of micronized estradiol per tablet.
PlaceboDrug
Also called Inactive drug
A sugar tablet that does not contain any active medicine
| Study group | Role | What they receive |
|---|---|---|
| Tamoxifen | Active comparator | tamoxifen 10mg daily for 7 days Receives: Drug: Tamoxifen Citrate 10Mg Tab |
| Estradiol | Active comparator | estradiol 1mg daily for 7 days Receives: Drug: Estradiol |
| placebo | Placebo comparator | placebo daily for 7 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of bleeding free days
Number of days of no spotting or bleeding after initiation of first treatment until day of subsequent bleeding
Measured: Up to 28 days
Secondary outcomes (5)
Total number of bleeding free days
Total number of no spotting or bleeding days
Measured: Up to 24 weeks
Days to first re-treatment
Number of days between first and second use of medication
Measured: Up to 24 weeks
Total number of re-treatments
Total number of times participant used treatment medication
Measured: Up to 24 weeks
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.
Measured: Up to 24 weeks
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)
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2021
- Study startMay 2022 (estimated)
- Primary completionJun 2024 (estimated)
- Study completionDec 2024 (estimated)
Why it stopped: Anticipated funding was not received
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Vaginal BleedingStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frances Casey, MD, MPH, Principal investigator, VCU Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04933240
- Sponsor's protocol ID
- HM20021901
- Status last verified
- May 2022
- First submitted
- 14 Jun 2021
- Last updated
- 3 Jun 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 31176688Edelman 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.
PubMed 32649493Abdel-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.
PubMed 24146298Abdel-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.
PubMed 16307966DeCensi 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.
PubMed 30973790Buzdar 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.
PubMed 8270984Macpherson 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.
PubMed 10601100Leslie 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.
PubMed 17721273Archer 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.
PubMed 8982742Thomas 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.
PubMed 11041216Alvarez-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.
PubMed 8633669
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tamoxifen Versus Estradiol in the Prevention of Unscheduled Bleeding in Etonogestrel Implant Users, a Randomized Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT04933240
- Acronym / sponsor ID
- HM20021901
- Conditions
- Vaginal Bleeding
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Anticipated funding was not received
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- May 2022 (estimated)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 21 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tamoxifen | Active comparator | Drug: Tamoxifen Citrate 10Mg Tabtamoxifen 10mg daily for 7 days |
| Estradiol | Active comparator | Drug: Estradiolestradiol 1mg daily for 7 days |
| placebo | Placebo comparator | Drug: Placeboplacebo daily for 7 days |
Who may qualify
- Ages
- 15 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- within 6 months following vaginal or cesarean delivery
- within 6 weeks following abortion
- currently breastfeeding
- positive pregnancy test
- contraindications to tamoxifen or estrogen
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tamoxifen Citrate 10Mg TabAlso: NOLVADEXnonsteroidal 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. | Drug | Tamoxifen |
| EstradiolAlso: ESTRACEestradiol tablets for oral administration contains 1 mg of micronized estradiol per tablet. | Drug | Estradiol |
| PlaceboAlso: Inactive drugA sugar tablet that does not contain any active medicine | Drug | placebo |
Primary outcome
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
5 secondary outcomes
Total number of bleeding free days
Time frame: Up to 24 weeks
Days to first re-treatment
Time frame: Up to 24 weeks
Total number of re-treatments
Time frame: Up to 24 weeks
Satisfaction with bleeding
Time frame: Up to 24 weeks
Affects on daily life activities
Time frame: Up to 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
- Background: PubMed 31176688Mansour 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.
- Background: PubMed 32649493Edelman 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.
- Background: PubMed 24146298Abdel-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.
- Background: PubMed 16307966Abdel-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.
- Background: PubMed 30973790DeCensi 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.
- Background: PubMed 8270984Buzdar 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.
- Background: PubMed 10601100Macpherson 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.
- Background: PubMed 17721273Leslie 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.
- Background: PubMed 8982742Archer 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.
- Background: PubMed 11041216Thomas 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.
- Background: PubMed 8633669Alvarez-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frances Casey, MD, MPH principal investigator
VCU Health System
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tamoxifen Citrate 10Mg Tab and Estradiol in people with Vaginal Bleeding, run by Virginia Commonwealth University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of bleeding free days (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04933240, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2022; AzTrials last refreshed its copy on 8 Nov 2026.