Tranexamic Acid for Blood Pressure Control During Cesarean Delivery

(RateTXA Trial)

Overseen By Aislynn Sharrock, BSc

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of British Columbia

Must not be taking: Blood pressure meds, sedatives

Disqualifiers: Hypertension, TXA allergy, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how different rates of administering tranexamic acid, a medicine that helps control bleeding, affect blood pressure during cesarean deliveries. The goal is to determine if administering the medicine quickly over 1 minute or slowly over 10 minutes impacts blood pressure changes. The trial focuses on healthy pregnant individuals who are at least 34 weeks along and planning to have a C-section using spinal anesthesia. Individuals with high blood pressure or those taking medication affecting blood pressure are not suitable for this study. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

If you are taking medications for high blood pressure or medications that could alter blood pressure, you will need to stop taking them to participate in this trial.

What is the safety track record for tranexamic acid?

Studies have shown that tranexamic acid is safe for preventing excessive bleeding after childbirth. Research indicates it significantly reduces blood loss in women undergoing cesarean deliveries without increasing the risk of serious side effects. Many patients tolerate tranexamic acid well, and no evidence suggests it raises the risk of life-threatening complications. This treatment is already widely used and approved for managing postpartum bleeding, offering additional reassurance about its safety. Ongoing studies are testing the drug at different administration speeds, but the treatment itself remains well-established and considered safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Tranexamic acid is unique because it offers a potential new approach for managing blood pressure during cesarean deliveries, a critical time when maintaining stable blood pressure is essential. Unlike many other treatments that focus primarily on controlling bleeding, tranexamic acid may help stabilize blood pressure more effectively. Researchers are excited about this trial because it explores different administration speeds—rapid-rate over 1 minute and slow-rate over 10 minutes—to see which offers better outcomes. This could lead to more precise and effective blood pressure management during cesarean sections, enhancing safety for both mothers and babies.

What is the effectiveness track record for tranexamic acid in controlling blood pressure during cesarean delivery?

Studies have shown that tranexamic acid effectively reduces the risk of dangerous bleeding after childbirth by preventing blood clots from breaking down. Research indicates that 26.7% of women who took tranexamic acid experienced severe bleeding, compared to 31.6% of those who received a placebo. This suggests it can significantly lower the chances of heavy bleeding after giving birth. While tranexamic acid has proven effective in controlling bleeding after childbirth, this trial investigates how different administration speeds might affect blood pressure during cesarean deliveries. Participants will receive tranexamic acid either through rapid-rate administration over 1 minute or slow-rate administration over 10 minutes. No evidence suggests that tranexamic acid increases any risks, making it a safe option for managing bleeding. ^{3 6 7 8 9}

Who Is on the Research Team?

Anton Chau, MD MMSc

Principal Investigator

Department of Anesthesia BC Women's Hospital

Are You a Good Fit for This Trial?

This trial is for healthy pregnant women scheduled for cesarean delivery. Specific eligibility details are not provided, but typically participants would need to meet certain health standards and have no conditions that could interfere with the study.

Inclusion Criteria

I am 19 years old or older.

I am at least 34 weeks pregnant and planning a C-section with spinal anesthesia.

American Society of Anesthesiologists (ASA) Physical Status Class 2

Exclusion Criteria

Patients arriving late to the surgical day care with <90 min prior to scheduled cesarean delivery time resulting in potential delay for the operating room or inadequate time for consent and full execution of the protocol

Known allergic reaction or hypersensitivity to TXA or any other TXA homologue

I have taken medication recently that can affect my blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive tranexamic acid at different administration rates (1 minute vs. 10 minutes) during cesarean delivery under spinal anesthesia

Immediate

1 visit (in-person)

Observation

Participants are monitored for changes in blood pressure and side effects such as nausea, vomiting, and central nervous system effects

4 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tranexamic Acid

Trial Overview The study is testing how different rates of administering Tranexamic Acid (TXA) affect blood pressure in patients. It compares the effects when TXA is given over 1 minute versus over 10 minutes during a cesarean delivery.

How Is the Trial Designed?

Group I: Rapid-rate administration of TXA Active Control 1 Intervention

This group will be administered tranexamic acid over 1 minute

Group II: Slow-rate administration of TXA Active Control 1 Intervention

This group will be administered tranexamic acid over 10 minutes

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

Approved in United States as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in European Union as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries
• Hereditary angioedema

Approved in Canada as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in Japan as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

Neonates born to mothers with preeclampsia showed significantly lower levels of thromboxane A2 (TXA2) metabolites and a disrupted balance between TXA2 and prostacyclin (PGI2) compared to those born to normotensive mothers, indicating a potential impact on neonatal health.

The study found that this imbalance in prostanoid levels correlates with reduced cerebral blood flow resistance in neonates from preeclamptic pregnancies, suggesting that maternal preeclampsia may affect neonatal cerebral circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An imbalance between prostacyclin and thromboxane in relation to cerebral blood flow in neonates with maternal preeclampsia. Nishimaki, S., Seki, K.[2019]

LCB 2853 is a potent antagonist of the thromboxane A2/prostaglandin H2 receptors, effectively inhibiting platelet aggregation and vasoconstriction in both in vitro and in vivo studies, with an effective dose (ED50) of less than 1 mg/kg in various animal models.

The drug demonstrated a significant duration of action, lasting up to 6 hours when taken orally and 3 to 5 hours when administered intravenously, suggesting its potential for use in antithrombotic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiaggregant and antivasospastic properties of the new thromboxane A2 receptor antagonist sodium 4-[[1-[[[(4-chlorophenyl)sulfonyl]amino]methyl]cyclopentyl] methyl]benzeneacetate. Lardy, C., Rousselot, C., Chavernac, G., et al.[2014]

Patients who experienced nausea during cesarean delivery had longer and more severe hypotension compared to those who did not, indicating a link between hypotension and nausea.

Using the pre-spinal mean arterial pressure (MAP) as a baseline for managing blood pressure during spinal anesthesia can help maintain higher intraoperative blood pressure and potentially reduce maternal nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the Optimum Baseline Blood Pressure for Spinal Anesthesia to Guide Vasopressor Management for Elective Cesarean Delivery: A Case-Control Design. Kovacheva, VP., Armero, W., Zhou, G., et al.[2023]

The novel TXA2 receptor antagonist GR32191 effectively inhibits platelet aggregation and secretion by irreversibly binding to the TXA2/prostaglandin endoperoxide receptor, demonstrating its potential as a therapeutic agent in managing platelet-related disorders.

TXA2 mediates platelet activation through at least two distinct receptor-effector systems: one that activates phospholipase C for aggregation and secretion, and another that increases cytosolic calcium for shape change, highlighting the complexity of platelet activation mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The response to thromboxane A2 analogues in human platelets. Discrimination of two binding sites linked to distinct effector systems. Takahara, K., Murray, R., FitzGerald, GA., et al.[2021]

In a study of 126 pregnant patients with severe preeclampsia undergoing cesarean sections, combined spinal-epidural anesthesia (CSEA) resulted in shorter operation and anesthesia onset times, as well as less intraoperative blood loss compared to total intravenous anesthesia (TIVA).

CSEA also led to better hemodynamic stability, higher Apgar scores for newborns, and a lower incidence of postoperative adverse reactions, indicating it is a safer and more effective anesthesia method for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Combined Spinal-Epidural Anesthesia and Total Intravenous Anesthesia on Hemodynamics and Pregnancy Outcomes of Severe Preeclampsia Pregnant Patients Undergoing Cesarean Section. Wang, G., Zhang, P., Li, M., et al.[2023]

Safety in spinal anesthesia for cesarean sections relies on careful patient evaluation and selection, ensuring that only suitable candidates undergo the procedure.

Key practices include using prophylactic vasopressors, maintaining systolic blood pressure above 100 mm Hg, and avoiding ergot compounds when vasopressors are used, which together help minimize risks during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal anesthesia for cesarean section. 1963. Moya, F., Smith, BE.[2019]

In a case of accidental intrathecal injection of tranexamic acid (TXA) during hip surgery, the patient experienced severe neurological and cardiac complications, highlighting the potential dangers of this medication when misadministered.

The treatment involving ventriculolumbar perfusion with saline and inhalational sedation with sevoflurane showed promise in managing TXA-induced neurotoxicity, suggesting a potential approach for similar cases, although complete recovery was not achieved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventriculolumbar perfusion and inhalational anesthesia with sevoflurane in an accidental intrathecal injection of tranexamic acid: unreported treatment options. Godec, S., Gradisek, MJ., Mirkovic, T., et al.[2022]

The study involved 50 pregnant women undergoing elective caesarean sections under spinal anaesthesia to assess the effectiveness of thrombo-embolic deterrent (TED) stockings in preventing hypotension.

While the use of TED stockings did not lead to a statistically significant difference in the incidence of hypotension or the need for ephedrine treatment compared to the control group, there was a trend suggesting that fewer women in the TED group required medication for hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thromboembolic deterrent stockings fail to prevent hypotension associated with spinal anaesthesia for elective caesarean section. Sood, PK., Cooper, PJ., Michel, MZ., et al.[2022]

Combined spinal and epidural anesthesia (CSE) using low doses of bupivacaine and fentanyl provides effective anesthesia for cesarean delivery in patients with severe preeclampsia, with 42 out of 46 patients achieving the desired sensory block without needing general anesthesia.

Both CSE for cesarean delivery and labor analgesia resulted in similar modest decreases in mean arterial pressure, which did not adversely affect neonatal outcomes, as indicated by comparable Apgar scores and umbilical artery pH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined spinal and epidural anesthesia with low doses of intrathecal bupivacaine in women with severe preeclampsia: a preliminary report. Ramanathan, J., Vaddadi, AK., Arheart, KL.[2019]

Intravenous or intra-arterial injections of U46619, a thromboxane A2 mimetic, caused a dose-dependent decrease in arterial blood pressure in anesthetized rats, indicating its potential as a vasodepressor agent.

The hypotensive effect of U46619 was significantly reduced by pretreatment with indomethacin or atropine, suggesting that its action is mediated through TxA2-receptor activation and involves the release of vasodilators like prostacyclin and acetylcholine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thromboxane-mimetic U46619 causes depressor responses in anaesthetized rats. Hui, SG., Ogle, CW.[2019]

The TXA2 receptor antagonist GR32191B effectively relaxes human internal mammary artery segments, showing up to 100% relaxation in response to specific vasoconstrictors, indicating its potential for improving arterial graft function in coronary bypass surgery.

In experiments, GR32191B significantly reduced contractions induced by vasoconstrictors like U46619 and PGF2 alpha, suggesting it could be a valuable therapeutic option to enhance graft patency and reduce vasoconstriction in arterial grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of thromboxane A2 antagonist GR32191B on prostanoid and nonprostanoid receptors in the human internal mammary artery. He, GW., Yang, CQ.[2019]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2028788

Tranexamic Acid for the Prevention of Blood Loss after ... The primary outcome occurred in 556 of 2086 women (26.7%) in the tranexamic acid group and in 653 of 2067 (31.6%) in the placebo group (adjusted ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06356948

Rate of Tranexamic Acid Administration on Blood Pressure ... This study aims to examine the effect of tranexamic acid administration rates on blood pressure changes over 1 minute compared to 10 minutes in healthy pregnant ...

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

Tranexamic acid for postpartum bleeding: a systematic ... Tranexamic acid reduces the risk of life-threatening postpartum bleeding. We found no evidence that tranexamic acid increases the risk of ...

4. withpower.com withpower.com/trial/phase-4-healthy-subjects-hs-2-2024-c7d64

Tranexamic Acid for Blood Pressure Control During ... This study aims to examine the effect of tranexamic acid administration rates on blood pressure changes over 1 minute compared to 10 minutes in healthy pregnant ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6891248/

Tranexamic acid for post-partum haemorrhage Tranexamic acid reduces bleeding by inhibiting the breakdown of blood clots. It is cost-effective and heat-stable with a long shelf life.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12128683/

Effect of Prophylactic Intraoperative Tranexamic Acid on ... Intraoperative TXA administration significantly reduces blood loss and the risk of PPH in women undergoing cesarean sections.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2207419

Tranexamic Acid to Prevent Obstetrical Hemorrhage after ... Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood ...

8. anestesiaobstetrica.com anestesiaobstetrica.com/CursoAnual/Public/UPLOAD/ARTICULOS/FILE-0000000011.pdf

Prophylactic tranexamic acid in Cesarean delivery Conclusion Prophylactic TXA administration for parturients undergoing Cesarean delivery significantly reduced blood loss, without increasing ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06604325?cond=Postpartum%20Hemorrhage&aggFilters=status:rec&rank=6

Prophylactic Tranexamic Acid To Reduce Blood Loss ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...