Pharmacokinetics and Pharmacodynamics of Tranexamic Acid in Women Having Caesarean Section Birth [WOMAN-PharmacoTXA]

Study Overview
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Brief Summary
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Intramuscular injection and oral solution of tranexamic acid (TXA) would increase its use in situations where administration of intravenous drugs is difficult. The investigators aim to assess the population pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous, intramuscular and oral TXA in women undergoing undergoing caesarean section (CS) with at least one known risk factor for postpartum haemorrhage (PPH)

Detailed Description
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An open label, randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral solution administration of tranexamic acid in women giving birth by caesarean section. 120 women (30 receiving oral liquid, 30 receiving intramuscular, 30 receiving intravenous and 30 receiving no TXA who have at least 6 evaluable PK samples will be randomised.

Official Title
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A Randomised Controlled Trial to Assess the Pharmacokinetics and Pharmacodynamics of Intramuscular, Intravenous and Oral Administration of Tranexamic Acid in Women Giving Birth by Caesarean Section

Conditions
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Pregnancy, High Risk

Intervention / Treatment
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* Drug: Tranexamic Acid 100Mg/Ml Inj Vil 10Ml
* Drug: Tranexamic Acid Oral Solution
* Drug: Tranexamic Acid Injectable Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women admitted to hospital giving birth by CS History of at least one risk factor for PPH Adult (≥18 years old) Exclusion Criteria: Women giving birth vaginally Women with a known allergy to TXA or its excipients Women with current antepartum haemorrhage Women known to have received TXA within 48 hours prior to randomisation Women with known renal impairment Women with any known blood clotting disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous tranexamic acid<br> | Drug: Tranexamic Acid 100Mg/Ml Inj Vil 10Ml<br>* 1 gram of tranexamic acid to be administered intravenously<br>|
| Experimental: Intramuscular tranexamic acid<br> | Drug: Tranexamic Acid Injectable Product<br>* 1 gram of tranexamic acid given as 2 separate intramuscular injection<br>|
| Experimental: Oral liquid tranexamic acid<br> | Drug: Tranexamic Acid Oral Solution<br>* 4 grams of tranexamic acid given as an oral solution<br>|
| No Intervention: No tranexamic acid<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic | Concentration of TXA in Maternal blood over time | 24 hours after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placenta transfer of TXA | Concentrations of TXA in placenta cord blood | at birth of baby | 
| Placenta transfer of TXA | Concentration of neonate TXA | within 24 hours of birth | 
| Concentration of D-dimer | Maternal blood concentration over time | up to 24 hours after randomisation | 
| Maternal blood volume lost | total blood loss | from incision to 2 hours from CS | 
| frequency of Injection site reaction from IM administration | Local reactions at injection site | from randomisation up to 7 days after | 
| Number of Adverse events (maternal and neonate) | any untoward medical events | from randomisation up to 7 days after | 
| Number of women with a clinical diagnosis of PPH | total blood loss of >1000 mL or any blood loss sufficient to cause haemodynamic instability or requires treatment | up to 24 hours after giving birth |