Tranexamic Acid for Postpartum Hemorrhage

(Optimum OB-TXA Trial)

Recruiting at 3 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

Trial Summary

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.

What data supports the effectiveness of the drug Tranexamic Acid for postpartum hemorrhage?

Research shows that Tranexamic Acid can reduce the risk of death from bleeding in cases of postpartum hemorrhage. It is recommended by the World Health Organization as a first-line treatment for this condition, indicating its effectiveness in managing severe bleeding after childbirth. ^{1 2 3 4 5}

Is tranexamic acid generally safe for humans?

Tranexamic acid is generally safe for humans when used correctly, as studies have shown no harmful effects on the liver, kidney, or heart. However, there have been serious safety concerns when it is mistakenly given in the wrong way during surgeries, leading to severe reactions like convulsions. ^{6 7 8 9 10}

How is the drug tranexamic acid unique in treating postpartum hemorrhage?

Tranexamic acid is unique because it is an antifibrinolytic agent that helps reduce bleeding-related deaths when given shortly after childbirth, and it is recommended by the World Health Organization as a first-line treatment for postpartum hemorrhage. Unlike some other treatments, it is administered intravenously and is particularly effective when used within 1 to 3 hours after delivery. ^{5 11 12 13 14}

What is the purpose of this trial?

In part 1 of the study, the investigators conducted a prospective, open-label, dose finding pharmacokinetic (PK) study in 43 pregnant 3rd trimester women scheduled for non-emergent cesarean section. The investigators administered three doses of the drug (5 mg/kg, 10 mg/kg and 15 mg/kg) in an escalating fashion by cohort with the lowest dose first. The drug was administered intravenously at the time of umbilical cord clamping for a non-emergent cesarean section. A maximum of 1 gram was administered. TXA serum levels at several time points after delivery were assayed to see if they reach the target plasma concentration of 10 microg/mL. A PK model was constructed for determining the optimal TXA dose administered at parturition. In part 2 of the study, the investigators aim to compare PKPD endpoints using prophylactic TXA via IV and IM routes administered pre-cord clamp. The investigators will administer 1000 mg TXA within 10 minutes of skin incision via intravenous infusion (up to n=15), intravenous bolus \< 2 minutes (up to n=15) and intramuscular injection (up to n=15). The investigators will target women undergoing scheduled cesarean delivery greater than 34 weeks gestation, women undergoing vaginal delivery \> 34 weeks of gestation and morbidly obese women (BMI\>=40) undergoing either a vaginal or cesarean delivery. The investigators will use advanced modeling techniques to determine time to achieve PKPD targets and duration remaining at those targets. The goal will be to determine how the optimal dose may vary if route of administration is modified. The investigators plan to enroll 45 patients in addition to the 43 that were enrolled during part 1. Our goal is to 30 participants, but the investigators will enroll 45 to account for lost to follow-up. The investigatorsalso aim to enroll 30 patients undergoing vaginal delivery and 30 morbidly obese women (BMI \> 50) undergoing either a vaginal or cesarean delivery but the investigators will enroll 45 patients for each of these groups to account for loss to follow up. In addition, the investigators will enroll 30 pregnant patients receiving no medication acting as the control group, but the investigators will enroll 45 to account for loss to follow up.

Research Team

Homa K Ahmadzia, MD

Principal Investigator

Inova Health Care Services

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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 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 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]

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 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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. England 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. [2023]

4. England 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. [2021]

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

Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis. [2022]

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

Tranexamic acid at cesarean delivery: drug-error deaths. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid at cesarean delivery: drug-error deaths. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Tranexamic acid at cesarean delivery: drug-error deaths. [2022]

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

Tranexamic acid at cesarean delivery: Drug-error deaths. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid for childbirth: why, when, and for whom. [2020]

12. Ireland pubmed.ncbi.nlm.nih.gov

Tranexamic acid versus misoprostol for management of postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials. [2023]

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

Does tranexamic acid reduce mortality in women with postpartum hemorrhage? [2020]

14. England pubmed.ncbi.nlm.nih.gov

Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. [2021]