Tranexamic Acid for Prevention of Postpartum Haemorrhage: a Dose-finding Study

NCT03565276 | Completed Phase 3

• 1 other identifier: 18-0001-A (MSH-REB)
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Published trials on tranexamic acid (TxA) for prevention have used a variety of fixed (0.5gm or 1gm) and body-weight adjusted (10mg/kg or 15mg/kg) doses of TxA. Given the wide range of bodyweights of pregnant women in contemporary obstetric practice, it is critical to determine the minimum effective dose of TxA, so as to avoid under- or over-dosing. The rationale of this study is to determine the minimum effective dose of TxA that is required to attain therapeutic plasma levels of TxA, established at 5-15mg/L, following administration of a single dose of intravenous (IV) TxA after childbirth and the clamping the umbilical cord, and before delivery of the placenta. Following birth of the infant, and upon clamping the umbilical cord, the investigators will administer a single dose of IV TxA in 100ml of 0.9% sodium chloride at 50mg/min according to the dose-escalation schedule described below. The slow rate of infusion has been chosen to prevent untoward effects such as hypotension that have been noted when the rate of infusion has exceeded 100mg/min. As part of the dose-escalation design, the investigators will start with 5mg/kg, half the smallest described dose, on a sample of up to 5 women. They will continue to administer TxA doses in increments of 5mg/kg to each successive batch of 5 women. If the number of treatment successes cannot statistically rule out a value \< 75% (\< 4 of 5 women are successes due to values in the low range), the dose will be increased by 5mg/kg for the next set of 5 women, and so on, until a maximum dose of 30mg/kg is reached, a dose deemed safe based on earlier studies in different populations. Once treatment success is determined at a certain dose, i.e. 4/5 women have levels in the therapeutic range), a total of 20 women will be administered that dose to ensure that 75% i.e. 18/20 women are successes at that dose.

Conditions

Post Partum Hemorrhage

Keywords

Post partum hemorrhage; Tranexamic acid; TXA; Dose-finding; Prevention

Outcome Measures

Primary Outcomes (1)

• Plasma levels of TxA

  Measured in mg/L. The 3 samples drawn at 15, 30 and 60 minutes should be between 5-15mg/L to be considered treatment success. Levels at 0 minutes is expected to be zero and 120 minutes expected to be sub-therapeutic.

  0, 15, 30, 60, 120 minutes

Secondary Outcomes (2)

• Early Adverse events

  maximum 24 hours

• Early adverse event 2 - Ga

  six weeks

Study Arms (1)

Experimental: TXA

EXPERIMENTAL

Intravenous Tranexamic Acid beginning at 5mg/kg administered as part of a dose-escalation design.

Drug: Tranexamic Acid

Interventions

Tranexamic Acid DRUG

A single dose of intravenous TxA in 100ml of 0.9% sodium chloride at 50mg/min, via a dose-escalation design

Also known as: TxA, Cyklokapron

Experimental: TXA

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women 18 years of age or greater
• Pregnant with a single fetus
• Undergoing planned caesarean delivery for a non-medical indication
• ≥ 37 completed weeks of gestation

You may not qualify if:

• Contraindications to use of TxA (i.e. acute arterial/venous thrombosis, hypersensitivity to TxA, history of seizures, moderate to severe renal failure from any condition, defective colour vision, subarachnoid haemorrhage and disseminated intravascular coagulation (abnormally increased activation of pro-coagulant pathways))
• Medical conditions that could influence bleeding and/or the pharmacokinetics of TxA (i.e. personal/family history of bleeding disorders, receipt of warfarin seven days or heparin 24 hours prior to caesarean delivery, hypertensive disorders of pregnancy, need for intra- or post-operative blood transfusions and postpartum thromboprophylaxis)
• Women with morbidly adherent placentae scheduled for planned caesarean-hysterectomies
• Use of concomitant medications that could result in drug interactions (hydrochlorothiazide, desmopressin, sulbactam-ampicillin, carbazochrome, ranitidine or nitroglycerin)

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Sinai Health System: collaborator
• University of Toronto: collaborator
• University of Waterloo: collaborator
• University Health Network, Toronto: collaborator

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1Z5, Canada

Location

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Tranexamic Acid

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

Study Officials

• Rohan D'Souza

  Rohan.Dsouza@sinaihealthsystem.ca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Maternal-Fetal Medicine Physician

Model Details: As part of the dose-escalation design, the investigators will start with 5mg/kg, half the smallest described dose, on a sample of up to 5 women. They will continue to administer TxA doses in increments of 5mg/kg to each successive batch of 5 women. If the number of treatment successes cannot statistically rule out a value \< 75% (\< 4 of 5 women are successes due to values in the low range), the dose will be increased by 5mg/kg for the next set of 5 women, and so on, until a maximum dose of 30mg/kg is reached, a dose deemed safe based on earlier studies in different populations. Once treatment success is determined at a certain dose, i.e. 4/5 women have levels in the therapeutic range), a total of 20 women will be administered that dose to ensure that 75% i.e. 18/20 women are successes at that dose.

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: June 21, 2018
• Study Start: July 11, 2018
• Primary Completion: March 14, 2019
• Study Completion: August 19, 2019
• Last Updated: September 23, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)