Tranexamic Acid for Postpartum Hemorrhage

(Optimum OB-TXA Trial)

Recruiting at 4 trial locations

Overseen By Jaclyn Phillips, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Inova Health Care Services

Must not be taking: Anti-fibrinolytics

Disqualifiers: Thromboembolic disease, Seizure disorder, Renal dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of tranexamic acid to prevent excessive bleeding after childbirth, focusing on different administration methods during cesarean or vaginal deliveries. Researchers aim to determine whether an IV or a shot is more effective in stopping postpartum hemorrhage (heavy bleeding after giving birth). The trial includes women scheduled for cesarean sections, those planning vaginal deliveries, and those who are morbidly obese. Participants must be pregnant, more than 34 weeks along, and have no kidney issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that tranexamic acid (TXA) is generally safe and effective in reducing severe bleeding after childbirth. Studies indicate that TXA significantly lowers the risk of death from bleeding in women who experience heavy postpartum bleeding. This represents a major finding from recent research.

Regarding safety, large studies have found that TXA does not significantly increase the risk of serious side effects. Some mild side effects, such as nausea or diarrhea, can occur. Importantly, the FDA has already approved TXA for other uses, which adds confidence in its safety.

Overall, TXA has been used safely in many patients and has demonstrated clear benefits in reducing bleeding and related deaths after childbirth. This makes it a promising option for managing heavy postpartum bleeding. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for postpartum hemorrhage?

Tranexamic acid is unique because it directly targets the excessive bleeding that can occur after childbirth, known as postpartum hemorrhage. Unlike other treatments that might involve surgical interventions or blood transfusions, tranexamic acid works by stabilizing blood clots, helping to reduce blood loss quickly and effectively. Researchers are excited about this treatment because it could offer a faster, less invasive way to manage bleeding, potentially saving lives and reducing the need for more complex procedures.

What evidence suggests that tranexamic acid might be an effective treatment for postpartum hemorrhage?

Research has shown that tranexamic acid (TXA) helps reduce dangerous bleeding after childbirth. The WOMAN trial found that TXA significantly lowered the risk of severe bleeding. Another analysis showed that TXA reduced total blood loss in women undergoing both cesarean and vaginal births. In this trial, participants will be divided into different groups, including those undergoing cesarean delivery, vaginal delivery, and those who are morbidly obese, to assess the effectiveness of TXA. Specifically, the WOMAN trial demonstrated that TXA decreased the amount of blood lost during surgery by about 344 milliliters compared to a placebo. These findings suggest TXA is a promising option for managing heavy bleeding after childbirth. ^{6 7 8 9 10}

Who Is on the Research Team?

Homa K Ahmadzia, MD

Principal Investigator

Inova Health Care Services

Are You a Good Fit for This Trial?

This trial is for women aged 18-50, over 34 weeks pregnant, undergoing elective cesarean or vaginal delivery. It includes morbidly obese women (BMI > 50). Participants must have normal kidney function and no history of thrombosis, liver dysfunction, seizure disorders, multiple gestations, or color vision defects.

Inclusion Criteria

I am over 34 weeks pregnant and planning a vaginal birth.

I am a woman scheduled for a C-section after 34 weeks of pregnancy.

Pregnant women with normal serum creatinine (serum creatinine < 0.9)

Exclusion Criteria

I have a genetic condition or another illness that increases my risk of blood clots.

I am a woman who has had a bleeding in the space around my brain.

I have developed color vision problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Part 1

Prospective, open-label, dose finding pharmacokinetic (PK) study in pregnant women scheduled for non-emergent cesarean section. TXA administered intravenously at the time of umbilical cord clamping.

1 day

1 visit (in-person)

Treatment Part 2

Comparison of PKPD endpoints using prophylactic TXA via IV and IM routes administered pre-cord clamp. TXA administered within 10 minutes of skin incision.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Plasma and breast milk sampling at various time points post-administration.

10-18 hours

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tranexamic acid

Trial Overview The study tests Tranexamic acid (TXA) to prevent postpartum hemorrhage. Part one determined the optimal dose; part two compares how TXA works when given through IV or IM before cord clamping in different patient groups including a control group with no medication.

How Is the Trial Designed?

Group I: Vaginal Delivery Experimental Treatment 2 Interventions

Group II: Morbidly Obese Experimental Treatment 2 Interventions

Group III: Cesarean Delivery Experimental Treatment 2 Interventions

Group IV: No TXA Active Control 1 Intervention

Tranexamic acid is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Lysteda for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma

Approved in European Union as Cyklokapron for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma
• Postpartum hemorrhage

Approved in Japan as Nicolda for:

• Heavy Menstrual Bleeding
• Menstrual Disorders
• Bleeding Disorder
• Factor IX Deficiency
• Hemophilia A
• Melasma
• Postpartum hemorrhage

Who Is Running the Clinical Trial?

Inova Health Care Services

Lead Sponsor

Trials

80

Recruited

22,700+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

George Washington University

Collaborator

Trials

263

Recruited

476,000+

Published Research Related to This Trial

A systematic review of 10 randomized controlled trials involving 2121 patients found that tranexamic acid (TXA) and misoprostol had no significant differences in their effectiveness for managing postpartum hemorrhage (PPH), including measures like intraoperative blood loss and hemoglobin change.

Both TXA and misoprostol demonstrated comparable safety profiles, with no significant differences in minor side effects and no thromboembolic events reported in the TXA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid versus misoprostol for management of postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials. Abu-Zaid, A., Baradwan, S., Albouq, B., et al.[2023]

Administering 1 g of intravenous tranexamic acid within 1 to 3 hours after delivery significantly reduces maternal mortality due to postpartum hemorrhage (PPH).

This finding is supported by strong evidence from randomized controlled trials and a Cochrane review, indicating that tranexamic acid is an effective intervention when used alongside standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does tranexamic acid reduce mortality in women with postpartum hemorrhage? Dresang, L., Kredit, S., Vellardita, L.[2020]

Tranexamic acid, when administered early (within 3 hours) for postpartum hemorrhage, can significantly reduce maternal deaths and complications, preventing up to 16 deaths and 9 laparotomies in a theoretical cohort of 100,000 women.

The early use of tranexamic acid is not only effective in improving health outcomes but also cost-effective, leading to an estimated annual savings of $23.15 million in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis. Howard, DC., Jones, AE., Skeith, A., et al.[2022]

Tranexamic acid is effective in treating postpartum hemorrhage, but there have been increasing reports of serious errors where it was mistakenly administered intrathecally instead of local anesthetic, leading to severe neurotoxicity and a high mortality rate of 50%.

To prevent these catastrophic errors, it is crucial to implement safety measures such as storing tranexamic acid separately from anesthetics and raising awareness among healthcare providers, as current alerts from health organizations have not sufficiently mitigated the risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid at cesarean delivery: drug-error deaths. Moran, NF., Bishop, DG., Fawcus, S., et al.[2022]

Tranexamic acid is effective in reducing bleeding-related mortality in women experiencing postpartum hemorrhage (PPH) when given shortly after delivery, with a recommended dosage of 1g intravenously, followed by a second dose if necessary.

Despite its effectiveness in treating PPH, there is insufficient evidence to support the routine use of tranexamic acid for preventing PPH after vaginal or cesarean deliveries, and monitoring for potential severe adverse events, like renal failure, is advised in high-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid for childbirth: why, when, and for whom. Sentilhes, L., Madar, H., Mattuizzi, A., et al.[2020]

A systematic review of 26 trials involving 4191 women found no reliable evidence that tranexamic acid (TXA) prevents postpartum haemorrhage during childbirth.

Many of the trials were of low quality, with serious flaws such as inadequate randomization and data inconsistencies, raising concerns about the validity of the findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. Ker, K., Shakur, H., Roberts, I.[2021]

Tranexamic acid is effective in treating postpartum hemorrhage, but there have been increasing reports of serious errors where it was mistakenly administered intrathecally instead of local anesthetics, leading to severe neurotoxicity and a high mortality rate of 50%.

To prevent these catastrophic errors, it is crucial to implement safety measures such as storing tranexamic acid separately from anesthetics and raising awareness among healthcare providers, as current alerts from health organizations have not sufficiently mitigated the risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid at cesarean delivery: drug-error deaths. Moran, NF., Bishop, DG., Fawcus, S., et al.[2023]

Tranexamic acid is effective in treating postpartum hemorrhage, but there have been increasing reports of serious errors where it was mistakenly administered intrathecally instead of local anesthetic, leading to severe neurotoxicity and a high mortality rate of 50%.

To prevent these catastrophic errors, it is crucial to implement safety measures such as storing tranexamic acid separately from anesthetics and raising awareness among healthcare providers, as current safety alerts have not been sufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid at cesarean delivery: drug-error deaths. Moran, NF., Bishop, DG., Fawcus, S., et al.[2023]

Tranexamic acid is effective in treating postpartum hemorrhage, but there have been increasing cases of it being mistakenly administered intrathecally instead of local anesthetics, leading to severe neurotoxicity and a high mortality rate of 50%.

To prevent these tragic errors, it is crucial to implement safety measures such as storing tranexamic acid separately from anesthetics and raising awareness among healthcare providers, as current alerts from health organizations have not been sufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid at cesarean delivery: Drug-error deaths. Moran, NF., Bishop, DG., Fawcus, S., et al.[2022]

In a study of 400 first-time mothers, tranexamic acid (Transamin) significantly reduced postpartum blood loss compared to no treatment, with the 1.0 g dose showing the best results.

The incidence of postpartum hemorrhage was lower in the groups receiving Transamin (6.4% for 1.0 g and 13.3% for 0.5 g) compared to the control group (25.3%), indicating its efficacy and safety without major adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study on the efficacy of tranexamic acid in reducing postpartum blood lose: a randomized, comparative, multicenter trial]. Yang, H., Zheng, S., Shi, C.[2022]

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]

In a double-blind trial involving patients with hemophilia and Christmas disease, tranexamic acid (1 g three times a day for five days) significantly reduced blood loss and the need for blood transfusions after dental extractions.

The study found no side effects or toxic effects on the liver, kidney, or heart, indicating that tranexamic acid is a safe option for managing bleeding in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. Forbes, CD., Barr, RD., Reid, G., et al.[2019]

Placenta previa affects about 4 in 1000 pregnancies and can lead to serious complications like bleeding and emergency cesarean sections, highlighting the need for effective management strategies.

This systematic review aims to evaluate the use of tranexamic acid (TXA) as a potential treatment for antepartum hemorrhage in placenta previa, focusing on its efficacy in preventing preterm birth and other perinatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tranexamic acid (TXA) to reduce preterm birth and other adverse obstetrical outcomes among pregnant individuals with placenta previa: a systematic review protocol. Seguin, N., Visintini, S., Muldoon, KA., et al.[2023]

Tranexamic acid is effective in reducing deaths from bleeding in trauma patients, regardless of their baseline risk of death, as shown in a meta-analysis of over 28,000 patients.

The use of tranexamic acid does not increase the risk of vascular occlusive events, making it a safe option for patients across all risk categories, including those with low and intermediate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients. Ageron, FX., Gayet-Ageron, A., Ker, K., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39812173/

Tranexamic acid for preventing postpartum haemorrhage ... TXA likely results in little to no difference in maternal satisfaction. These findings are based mainly on two large trials. In the smaller of ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)02102-0/fulltext

Tranexamic acid for postpartum bleeding: a systematic ... We found strong evidence that tranexamic acid reduces life-threatening bleeding. This result was mainly driven by data from the WOMAN trial,.

3. bmcpregnancychildbirth.biomedcentral.com bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-023-06100-8

Efficacy and safety of tranexamic acid in prevention of ... This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0333177

Efficacy of prophylactic tranexamic acid among parturient at ... The meta-analysis revealed that TXA significantly reduces intraoperative blood loss compared to placebo (Mean Difference (MD) = −343.89, 95% CI [−394.34, − ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05562609

Study Details | NCT05562609 | Tranexamic Acid to Prevent ... The trial will assess the effects of intramuscular (IM) and intravenous (IV) tranexamic acid on PPH, side effects and other important maternal health outcomes.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK532909/

Tranexamic Acid - StatPearls - NCBI Bookshelf The data revealed reduced rebleeding and mortality compared to the group not treated with TXA.[14]. Postpartum hemorrhage: The WOMAN Trial ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10668444/

Efficacy and safety of tranexamic acid in prevention ... In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03287336

Prevention of Postpartum Hemorrhage With Tranexamic Acid TXA has recently been proven to reduce mortality when given to women in setting of diagnosed PPH. US obstetricians and anesthesiologists are hesitant to use TXA ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1800942

Tranexamic Acid for the Prevention of Blood Loss after ... Tranexamic acid was recently shown to reduce bleeding-related mortality among women with postpartum hemorrhage, especially when the drug was administered ...

10. ajogmfm.org ajogmfm.org/article/S2589-9333(22)00154-9/fulltext

Tranexamic acid for bleeding: Much more than a treatment ... The evidence that early tranexamic acid treatment reduces postpartum hemorrhage deaths has major implications for obstetrical care worldwide.