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

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

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)

Study Overview

• Status: Completed
• Conditions: Pregnancy, High Risk
• Intervention / Treatment: Drug: Tranexamic Acid 100Mg/Ml Inj Vil 10Ml; Drug: Tranexamic Acid Injectable Product; Drug: Tranexamic Acid Oral Solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Pakistan
  • Islamabad, Pakistan
    • MCH PIMS
• Zambia
  • Lusaka, Zambia
    • Women and Newborn Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Rawalpindi Medical College
• Investigators: Study Chair: Haleema Shakur-Still, London School of Hygiene and Tropical Medicine; Study Chair: Ian Roberts, London School of Hygiene and Tropical Medicine

Publications and helpful links

General Publications

• Arribas M, Roberts I, Chaudhri R, Geer A, Prowse D, Lubeya MK, Kayani A, Javaid K, Grassin-Delyle S, Shakur-Still H. WOMAN-PharmacoTXA trial: Study protocol for 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. Wellcome Open Res. 2021 Jun 16;6:157. doi: 10.12688/wellcomeopenres.16884.1. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 2020-KEP-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Totally anonymised dataset used for main analysis will be made freely available
• IPD Sharing Time Frame: freely available 1 year after main publication
• IPD Sharing Access Criteria: Free login to website required for monitoring usage of data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No