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

48 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Tranexamic Acid for contraceptive-related bleeding?

Research shows that Tranexamic Acid (TXA) is effective in controlling irregular uterine bleeding in users of contraceptives like Norplant and DMPA. Additionally, TXA is commonly used to treat heavy menstrual bleeding and has been shown to reduce blood loss in various medical situations. ^{1 2 3 4 5}

How does the drug tranexamic acid differ from other treatments for contraceptive-related bleeding?

Tranexamic acid (TXA) is unique because it works by preventing the breakdown of blood clots, which helps reduce bleeding. Unlike other treatments, TXA can be administered in various forms, including oral, intravenous (IV), and intramuscular (IM), offering flexibility in how it is used. This makes it a versatile option for managing bleeding related to contraceptive use. ^{3 6 7 8 9}

What is the purpose of this trial?

This randomized double blinded trial seeks to determine whether tranexamic acid (TXA) is an efficacious treatment for contraceptive induced menstrual changes (CIMC) including irregular, bothersome bleeding caused by the etonogestrel subdermal contraceptive implant (ENG implant). Participants will be randomized into the TXA treatment arm or a placebo. They will begin taking the medication after three consecutive days of bleeding. Participants will track their bleeding using an automated text message service

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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) 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) 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effect of tranexamic acid for treatment of irregular uterine bleeding secondary to Norplant use. [2013]

2. Thailand pubmed.ncbi.nlm.nih.gov

The effect of tranexamic acid for treatment irregular uterine bleeding secondary to DMPA use. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Tranexamic acid evidence and controversies: An illustrated review. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Tranexamic Acid Update in Trauma. [2017]

5. United States 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. [2021]

6. England 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Tranexamic acid for the prevention of postpartum bleeding: Protocol for a systematic review and individual patient data meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid in gynecologic surgery. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of tranexamic acid after intravenous, intramuscular, and oral routes: a prospective, randomised, crossover trial in healthy volunteers. [2022]