Efficacy of Tranexamic Acid in Preventing Postpartum Haemorrhage After Elective Caesarean Section

NCT03463993 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ETAPPPH
• Study Type: interventional
• Target: 506
• Locations: 1 country
• Sites: 2

Brief Summary

Background Postpartum haemorrhage (PPH) is a major cause of maternal mortality worldwide accounting for 25% of maternal deaths. In Zimbabwe PPH is the second most common cause of death. Tranexamic acid (TXA) is widely used to reduce blood loss in elective surgery, bleeding trauma patients, and menorrhagia. The investigators seek to determine the efficacy of TXA in reducing PPH during and after elective caesarean section. Methods and Design The investigators intend to perform an open label randomized control study of 1,162 women who are undergoing elective caesarean section. The participants will be randomly selected to receive an intravenous infusion of TXA 10 minutes prior to skin incision or not to receive the intervention. Prophylactic oxytocin will be administered to all the women. The primary outcome will be incidence of PPH defined by blood loss equal to or more than 1,000ml calculated by determining the difference in haematocrit values taken prior to and 48 hours after caesarean section. Discussion In addition to prophylactic uterotonic administration, TXA is a complementary component acting on the haemostatic process that can be used in the third stage of labour to prevent PPH. It is a promising intervention that is cheap, easy to administer and would be easy to add to routine delivery protocols in hospitals. It would also help to conserve precious resources by reducing the need for blood products, and expensive surgical interventions to manage PPH. This large adequately powered randomized study seeks to determine the efficacy of TXA to validate its routine use at caesarean section to prevent PPH.

Conditions

Post Partum Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Postpartum Haemorrhage (PPH)

  PPH based on Haematocrit calculation and PPH based on Haemoglobin calculation

  Up to 48 hours post-caesarean section

Secondary Outcomes (12)

• Estimated Blood Loss

  At caesarean section

• Amount of Blood Transfused

  At caesarean section up to 48 hours post-caesarean section

• Number of Participants With Use of Additional Uterotonics

  At caesarean section up to 48 hours post-caesarean section

• Number of Participants With Tranexamic Acid Side Effects

  From intravenous infusion of the drug up to 48 hours post-caesarean section

• Number of Participants Requiring Emergency Surgery for PPH

  At caesarean section up to 48 hours post-caesarean section

Study Arms (2)

Group A

EXPERIMENTAL

Participants receive a low dose of Tranexamic acid (10mg/kg) administered slowly over 5 minutes intravenously (iv) 10 minutes prior to skin incision in elective caesarean section with prophylactic oxytocin (5 IU iv) slow administration on delivery of the baby.

Drug: Tranexamic Acid; Drug: Oxytocin

Group B

ACTIVE COMPARATOR

Participants receive prophylactic oxytocin (5 IU iv) slow administration on delivery of the baby

Drug: Oxytocin

Interventions

Tranexamic Acid DRUG

TXA (10mg/kg) solution for injection from the vial will be diluted with 100 - 200ml electrolyte solution such as Normal Saline, Ringers solution, dextrose/water for injection on the same day it is to be used (i.e. when anaesthetist notes the patient has been randomized to receive TXA). Intravenous administration should be at a rate of 100mg or fraction thereof over at least 1 minute - usually at least 5 minutes. Standard practice is to administer over 20 minutes. Administration is to be done at least 10 minutes prior to skin incision.

Also known as: TXA

Group A

Oxytocin DRUG

5IU of oxytocin are administered intravenously slowly once the baby has been delivered at caesarean section.

Also known as: Prophylactic oxytocin

Group A; Group B

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant woman with signed informed consent\*\*\*
• Understand English and/or Shona
• Estimated gestational age of 38 weeks or older
• Requiring Elective Caesarean Section defined as caesarean section performed before onset of labour
• Live intrauterine fetus

You may not qualify if:

• Placental Abruption
• Emergency caesarean section
• Current or previous history of significant disease including heart disease, liver, renal disorders
• Known coagulopathy or history of deep venous thrombosis and/or pulmonary embolism, or arterial thrombosis (angina pectoris, myocardial infarction, stroke)
• History of epilepsy or seizures
• Autoimmune disease
• Sickle cell disease
• Severe haemorrhagic disease
• Intrauterine fetal demise
• Eclampsia/HELLP syndrome
• Administration of anticoagulants - clexane or antiplatelet agents in the week prior to delivery

Sponsors & Collaborators

• University of Zimbabwe: lead

Study Sites (2)

Harare Central Hospital

Harare, Zimbabwe

Location

Parirenyatwa Group of Hospitals

Harare, Zimbabwe

Location

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Tranexamic Acid; Oxytocin

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The a priori power was not been achieved as the target sample size had not yet been achieved due to reasons beyond the scope of the study. The study had no placebo and was not blinded.

Results Point of Contact

• Title: Dr Chipo Gwanzura
• Organization: University of Zimbabwe

chipo.gwanzura@gmail.com

+263774718381

Study Officials

• Tsungai Chipato, MBChB FRCOG

  Professor of Obstetrics and Gynaecology

  STUDY CHAIR

• Taazadza Nhemachena, MBChB MMED

  Lecturer and Consultant

  STUDY CHAIR

• Chipo Gwanzura, MBChB

  Registrar

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Trial is an open label randomized control trial
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Junior Registrar

Model Details: Randomized control trial with two arms. Participants receive either 10mg/kg of TXA 10 minutes prior to elective caesarean section with prophylactic oxytocin administration after delivery of the baby, versus prophylactic oxytocin alone after delivery of the baby.

Study Record Dates

• First Submitted: February 17, 2018
• First Posted: March 13, 2018
• Study Start: April 8, 2018
• Primary Completion: December 31, 2018
• Study Completion: June 30, 2019
• Last Updated: June 1, 2022
• Results First Posted: April 20, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: TBA
• Access Criteria: Communicate with researcher on chipo.gwanzura@gmail.com

Locations

ZI (2)