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

Trial Summary

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 data supports the effectiveness of the drug Tranexamic Acid for blood pressure control during cesarean delivery?

Tranexamic Acid (TXA) is known to reduce bleeding-related deaths in trauma patients and is used in surgeries, which suggests it may help manage blood loss during cesarean delivery. However, there is no direct evidence from the provided research specifically linking TXA to blood pressure control during cesarean delivery. ^{1 2 3 4 5}

Is Tranexamic Acid (TXA) generally safe for use in humans?

Tranexamic Acid (TXA) is generally considered safe for use in humans, but there are rare cases where accidental injection into the spine can cause serious heart and nerve problems. It is important to use TXA as directed by healthcare professionals to avoid such risks. ^{1 2 3 4 6}

How does the drug Tranexamic Acid differ from other treatments for blood pressure control during cesarean delivery?

Tranexamic Acid is unique because it is primarily used to reduce bleeding by helping blood to clot, which is different from other treatments that focus on directly managing blood pressure. This makes it a novel approach for controlling blood pressure during cesarean delivery by potentially reducing the need for other medications that directly affect blood pressure. ^{7 8 9 10 11}

What is the purpose of this trial?

Tranexamic acid is a well-established treatment for post-partum hemorrhage. 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 patients scheduled for cesarean delivery.

Research Team

Anton Chau, MD MMSc

Principal Investigator

Department of Anesthesia BC Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ventriculolumbar perfusion and inhalational anesthesia with sevoflurane in an accidental intrathecal injection of tranexamic acid: unreported treatment options. [2022]

2. Germany 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. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Thromboxane-mimetic U46619 causes depressor responses in anaesthetized rats. [2019]

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

The response to thromboxane A2 analogues in human platelets. Discrimination of two binding sites linked to distinct effector systems. [2021]

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

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

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Thromboembolic deterrent stockings fail to prevent hypotension associated with spinal anaesthesia for elective caesarean section. [2022]

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

Combined spinal and epidural anesthesia with low doses of intrathecal bupivacaine in women with severe preeclampsia: a preliminary report. [2019]

9. United States 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. [2023]

10. United States 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. [2023]

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

Spinal anesthesia for cesarean section. 1963. [2019]