Tranexamic Acid for Contraceptive-Related Bleeding

Overseen By Women's Health Research Unit Department of Ob/Gyn

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Oregon Health and Science University

Must be taking: Etonogestrel implant

Must not be taking: Anticoagulants, NSAIDs, Oral contraceptives, others

Disqualifiers: Pregnancy, Renal insufficiency, Thromboembolism, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether tranexamic acid can effectively reduce irregular and bothersome bleeding caused by the etonogestrel subdermal contraceptive implant. Participants will receive either tranexamic acid, a medication used to reduce bleeding, or a placebo after three consecutive days of bleeding, and they will track their bleeding via text messages. It is ideal for individuals who have used the implant for over a month, experienced frequent or prolonged bleeding, and have access to a reliable cell phone. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using anticoagulants, certain drugs affecting the P450 pathway, or if you are using oral contraceptives without a 4-6 week break. If you use NSAIDs regularly or have chronic use of marijuana or cigarettes, you may need a washout period before joining.

What is the safety track record for tranexamic acid?

Research has shown that tranexamic acid (TXA) is generally safe for use. Studies have found that it reduces bleeding without increasing the risk of blood clots, reassuring those concerned about side effects. TXA has been successfully used in various medical situations, such as surgeries and controlling postpartum bleeding, with good results and few serious issues reported. Although limited information exists on the risk of blood clots when TXA is used with hormonal birth control, it is usually well-tolerated. This makes TXA a promising option for managing bleeding related to contraceptive implants. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about tranexamic acid for contraceptive-related bleeding because it offers a new approach by directly stabilizing blood clots, which can help reduce and manage bleeding more effectively. Unlike hormonal treatments that are typically used for this condition, tranexamic acid works by preventing the breakdown of fibrin, a protein essential for blood clotting. This not only provides a non-hormonal option for those who may experience side effects from hormonal therapies but also has the potential to deliver quicker results, possibly within just five days.

What evidence suggests that tranexamic acid might be an effective treatment for contraceptive-related bleeding?

Research has shown that tranexamic acid (TXA), which participants in this trial may receive, helps reduce bleeding from various causes. One study found that 68% of women using TXA for bleeding related to birth control experienced more than 20 days without bleeding, while none in the placebo group did. TXA also effectively reduces heavy menstrual bleeding. Importantly, TXA does not usually increase the risk of blood clots, making it a safer choice for managing bleeding. These findings suggest that TXA could be useful for controlling bleeding from contraceptive implants. ^{3 6 7 8 9}

Who Is on the Research Team?

Alison B Edelman, MD, MPH

Principal Investigator

Oregon Health and Science University

Leo Han, MD, MCR

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for people in good health who experience frequent or prolonged bleeding with an ENG contraceptive implant and have been using it for at least 30 days. Participants must not be pregnant, less than 6 months postpartum, or have certain medical conditions like a history of blood clots or liver issues.

Inclusion Criteria

I have a palpable etonogestrel contraceptive implant.

I have had long or frequent bleeding episodes with my ENG implant.

I am in good overall health.

Exclusion Criteria

Less than 6 months postpartum, less than 6 weeks abortion, not breast/chest feeding (cessation of lactation at least 6 weeks prior to enrollment)

Centers for Disease Control Medical Eligibility for Contraceptive use category 3 or 4 for contraceptive usage

I haven't smoked cigarettes for at least six months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tranexamic acid (TXA) or placebo for five days after three consecutive days of bleeding

5 days

Participants track bleeding using an automated text message service

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tranexamic Acid

Trial Overview The study tests if Tranexamic Acid (TXA) can help manage irregular bleeding caused by the ENG contraceptive implant. Half of the participants will receive TXA while the other half will get a placebo, without knowing which one they're taking.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

After three consecutive days of bleeding, five days of 1300mg TXA three times per day (TID).

Group II: Placebo Placebo Group 1 Intervention

After three consecutive days of bleeding, five days of placebo three times per day.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Bill and Melinda Gates Foundation

Collaborator

Trials

428

Recruited

23,060,000+

Published Research Related to This Trial

Tranexamic acid (TXA) effectively reduces blood loss and the need for blood transfusions in various gynecologic surgeries, including hysterectomy and myomectomy, based on randomized control trials involving hundreds of patients.

TXA works by binding to plasminogen, preventing the breakdown of blood clots, making it a safe and beneficial adjunct in surgical procedures to manage bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid in gynecologic surgery. Zakhari, A., Sanders, AP., Solnik, MJ.[2020]

Intramuscular (i.m.) administration of tranexamic acid (TXA) is a fast and complete alternative to intravenous (i.v.) administration, achieving target concentrations much quicker than oral administration, which was less effective in reaching the desired levels.

The study involved 15 healthy volunteers and found that adverse events from TXA administration were mild and transient, indicating a good safety profile for the i.m. route.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of tranexamic acid after intravenous, intramuscular, and oral routes: a prospective, randomised, crossover trial in healthy volunteers. Grassin-Delyle, S., Semeraro, M., Lamy, E., et al.[2022]

In a study of 100 women using depot-medroxyprogesterone acetate (DMPA) for contraception, tranexamic acid significantly reduced irregular uterine bleeding, with 88% of participants experiencing cessation of bleeding in the first week compared to only 8.2% in the placebo group.

After 4 weeks, 68% of women treated with tranexamic acid had a bleeding-free interval of over 20 days, while none in the placebo group achieved this, highlighting tranexamic acid's efficacy in managing abnormal bleeding associated with DMPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tranexamic acid for treatment irregular uterine bleeding secondary to DMPA use. Senthong, AJ., Taneepanichskul, S.[2016]

Tranexamic acid (TXA) is recommended for treating severe postpartum bleeding and may also be effective in preventing such bleeding when administered shortly before or after birth, potentially improving outcomes for many women.

A systematic review and individual patient data meta-analysis will assess the effectiveness and safety of TXA in preventing postpartum bleeding, focusing on life-threatening bleeding and thromboembolic events, with data from trials involving at least 500 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid for the prevention of postpartum bleeding: Protocol for a systematic review and individual patient data meta-analysis. Ker, K., Shakur-Still, H., Sentilhes, L., et al.[2023]

Tranexamic acid (TXA) is an effective antifibrinolytic agent used to prevent and treat various types of bleeding, including heavy menstrual bleeding and trauma, supported by a strong body of evidence from landmark randomized controlled trials.

Despite its proven efficacy, there remains hesitancy in its use due to concerns about potential risks, such as thrombosis, especially when prescribed with hormonal contraceptives or in patients with gross hematuria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid evidence and controversies: An illustrated review. Relke, N., Chornenki, NLJ., Sholzberg, M.[2023]

In a study involving 120 women undergoing caesarean sections, both intramuscular (IM) and oral tranexamic acid (TXA) were found to be well tolerated, with no serious adverse events reported for mothers or neonates.

Intramuscular TXA demonstrated a rapid onset of action, inhibiting fibrinolysis within 10 minutes, making it a suitable alternative to intravenous (IV) administration, while oral TXA took about an hour to reach therapeutic levels and is not recommended for emergency use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative routes for tranexamic acid treatment in obstetric bleeding (WOMAN-PharmacoTXA trial): a randomised trial and pharmacological study in caesarean section births. Shakur-Still, H., Roberts, I., Grassin-Delyle, S., et al.[2023]

Tranexamic acid (TXA) has been shown to significantly reduce mortality in trauma patients if administered within 3 hours of injury, highlighting its efficacy in emergency situations.

Further research is needed to determine the best dosing, timing, and mechanisms of TXA, as well as the potential use of real-time viscoelastic testing to improve patient selection for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic Acid Update in Trauma. Ramirez, RJ., Spinella, PC., Bochicchio, GV.[2017]

Prophylactic use of tranexamic acid (TXA) in high-risk obstetric patients undergoing cesarean delivery may significantly reduce both intraoperative and postoperative blood loss, based on a review of three trials with 203 patients.

TXA also appears to decrease the need for additional uterotonic therapy, suggesting it could be an effective intervention to manage postpartum hemorrhage, although it does not significantly impact postoperative hemoglobin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic Tranexamic Acid in High-Risk Patients Undergoing Cesarean Delivery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Stortroen, NE., Tubog, TD., Shaffer, SK.[2021]

In a study of 68 Norplant users with irregular bleeding, tranexamic acid significantly reduced bleeding episodes in the first week compared to placebo, with 64.7% of the tranexamic acid group experiencing cessation of bleeding versus 35.3% in the placebo group.

However, after 4 weeks, there was no significant difference in the overall bleeding-free interval between the tranexamic acid group (58.8%) and the placebo group (76.5%), indicating that while tranexamic acid is effective in the short term, it does not provide lasting benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tranexamic acid for treatment of irregular uterine bleeding secondary to Norplant use. Phupong, V., Sophonsritsuk, A., Taneepanichskul, S.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8614172/

Efficacy of Oral Tranexamic Acid Versus Combined ... The current study revealed that both oral tranexamic acid and COC pills were equally effective in reducing the mean blood loss among patients with HMB.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2475037922014091

Tranexamic acid evidence and controversies: An illustrated ... Tranexamic acid (TXA) decreases the risk of bleeding and often the risk of death from bleeding. · In general, TXA does not increase the risk of blood clots.

3. withpower.com withpower.com/trial/phase-4-hemorrhage-10-2023-45436

Tranexamic Acid for Contraceptive-Related Bleeding After 4 weeks, 68% of women treated with tranexamic acid had a bleeding-free interval of over 20 days, while none in the placebo group achieved this, ...

4. stacks.cdc.gov stacks.cdc.gov/view/cdc/214405/cdc_214405_DS1.pdf

Tranexamic Acid Treatment for Heavy Menstrual Bleeding Women with heavy menstrual bleeding treated with tranexamic acid achieved the prespecified three- part primary efficacy outcome. A statistically signifi ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/022430s009lbl.pdf

LYSTEDA® (tranexamic acid) tablets, for oral use The efficacy of LYSTEDA in the treatment of heavy menstrual bleeding (HMB) in women of reproductive potential was demonstrated in two randomized, double-blind, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2009/022430s000medr.pdf

Clinical Memo to NDA 22-430 Lysteda - eCopy, Inc. - FDA Postmarketing Commitment: There are limited data on the risk of thromboembolic events associated with the concomitant use of tranexamic acid and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8691851/

Concomitant use of combined hormonal contraceptives and ... Large randomized controlled trials have demonstrated that the use of tranexamic acid in trauma, postpartum hemorrhage and orthopedic surgeries – all very high- ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06000423

Study Details | NCT06000423 | Tranexamic Acid to Reduce ... Undiagnosed abnormal uterine bleeding pre-dating placement of contraceptive implant. Bleeding dyscrasia. Anticoagulation use. Active cervicitis.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8279901/

Tranexamic acid evidence and controversies: An illustrated ... Tranexamic acid (TXA) decreases the risk of bleeding and often the risk of death from bleeding. · In general, TXA does not increase the risk of blood clots.