The Efficacy of Tranexamic Acid in Preventing Postpartum Haemorrhage After Caesarean Section (ETAPPH)

This study seeks to determine if the using tranexamic acid prophylactically at caesarean section will prevent postpartum haemorrhage which is a major cause of maternal mortality in Zimbabwe and globally.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic acid injection; Other: Normal saline placebo

Detailed Description

This trial will be an placebo-controlled, two-centre, randomized control trial with two parallel groups including 1,162 women who undergo elective or emergency caesarean deliveries at term. The study group will receive tranexamic acid (TXA) 1g intravenously at the onset of skin incision. There is normal saline placebo for the control group. The study and control groups will both receive the standard care offered at caesarean section including 5 IU of oxytocin intravenously on delivery of the baby. .

• Study Type: Interventional
• Enrollment (Actual): 1226
• Phase: Phase 3

Contacts and Locations

Study Locations

• Zimbabwe
  • Harare, Zimbabwe
    • Parirenyatwa Group of Hospitals (Mbuya Nehanda Maternity Hospital)
  • Harare, Zimbabwe
    • Sally Mugabe Central Hospital Maternity Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: Women undergoing elective or emergency caesarean section with:

• Estimated gestational age of 37 weeks or more
• Live intrauterine foetus
• Elective or emergency caesarean delivery
• Signed informed consent

Exclusion Criteria:

• History of coagulopathies or conditions predisposing them to thromboembolic phenomena,
• seizure history,
• autoimmune disease,
• placental abruption,
• placenta praevia,
• abnormally adherent placentae if identified on prenatal ultrasound,
• eclampsia or HELLP syndrome,
• known hypersensitivity to TXA,
• planned general anaesthesia,
• caesarean delivery for the second twin or second/third triplet(s) after vaginal birth of the first twin,
• poor understanding of English/Shona languages,
• those who have received anticoagulants in the week before delivery
• persons-under-investigation for Coronavirus disease (COVID-19) and confirmed COVID-19 positive women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group/Group A; The study group will receive TXA 1g intravenously at the onset of skin incision.	Drug: Tranexamic acid injection; Tranexamic 1g administered intravenously at the onset of skin incision at caesarean section; Other Names: TXA
Placebo Comparator: Control group/Group B; There is an equivalent volume of normal saline for the control group.	Other: Normal saline placebo; 10ml of normal saline will be administered intravenously at onset of skin incision at caesarean section to the placebo group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Postpartum Hemorrhage (PPH)	Calculated estimated blood loss exceeding 1000ml. Estimated Blood Loss (EBL) was calculated using laboratory values of hemoglobin levels before and after procedure. Postpartum hemorrhage is defined as blood loss exceeding 1000mL after cesarean section.	Up to day 2 postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Loss Using Hemoglobin Values	Calculated blood loss using hemoglobin values. A mean value of blood loss calculated using hemoglobin values	Up to day 2 postpartum
Mean Blood Loss as Estimated by Obstetrician	Visually estimated blood loss at time of caesarean section. Attending obstetrician gave an estimated value of blood loss after delivery.	2 hours
Occurrence of Postpartum Shock	Number of participants who had hypovolemic shock related to PPH as determined by assessing BP and pulse.	Up to day 2 postpartum
Use of Supplementary Uterotonic(s)	Number of women requiring supplementary uterotonics	Up to day 2 postpartum
Postpartum Transfusion	Number of women given postpartum transfusion	Up to day 2 postpartum
Emergency Surgery for PPH	Number of participants who had emergency surgery for PPH including caesarean hysterectomies	Up to day 2 postpartum
Change in Peripartum Haemoglobin	Mean change in haemoglobin concentration between the study group, calculated hemoglobin values at day 2 postpartum minus baseline hemoglobin values.	Up to day 2 postpartum
Number of Participants With a Decrease in Peripartum Hemoglobin	Number of participants with a drop in hemoglobin more than 2g/dL or less than 2g/dL	Up to day 2 postpartum
Change in Peripartum Haematocrit	Mean change in haematocrit percentage between the study groups from baseline to day 2 postpartum	Up to day 2 postpartum
Admission Into Intensive Care Unit	Number of participants transferred to intensive care unit	Up to day 2 postpartum
Death From Any Cause	Number of participants who died from any cause	Up to date of death or day 4 from admission
Blood Pressure Measurements	Blood pressure at 15, 30, 45, 60, and 120 min after delivery	Up to 2 hours after the caesarean section
Number of Mild Adverse Events	Number of mild events of nausea, vomiting, sensation of rings or spots of light in the visual field, dizziness	Up to 24 hours after administration
Number of Severe Adverse Events	Deep vein thrombosis (if the diagnosis is confirmed by Doppler ultrasound); Pulmonary embolism (if the diagnosis is confirmed by radiological examination); Myocardial infarction; Seizure; Renal failure requiring dialysis	Up to day 3 postpartum
Any Other Unexpected Adverse Event	Number of unexpected events during and after the adminstration of study drug and duration of observation	Up to day 3 postpartum
Length of Hospital Stay	Duration of hospital admission in days	Up to day 3 postpartum

Collaborators and Investigators

• Sponsor: University of Zimbabwe
• Collaborators: Fogarty International Center of the National Institute of Health
• Investigators: Principal Investigator: Chipo Gwanzura, MD, University of Zimbabwe

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): December 14, 2021
• Study Completion (Actual): December 14, 2021

Study Registration Dates

• First Submitted: January 16, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Caesarean section; Prevent; Tranexamic acid; Postpartum hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: ETAPPH; D43TW009343 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is not yet known if there will be a plan to make individual patient data (IPD) available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes