Tranexamic Acid and Thromboelastography During Cesarean Delivery (TA TEG)

The Influence of Prophylactic Tranexamic Acid on Thromboelastography During Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Trial

The aim of this study is to characterize the coagulation changes, using thromboelastography (TEG), after prophylactic tranexamic administration during cesarean delivery. Specifically, TEG values will be compared in patients who receive prophylactic tranexamic acid or placebo before surgery, during elective cesarean delivery, and 2 hours postpartum.

Postpartum hemorrhage (PPH) is increasing in incidence in the United States, renewing interest in multimodal approaches to blood conservation during cesarean delivery. Pharmacologic therapy with the antifibrinolytic agent, tranexamic acid (TA), has been shown to reduce estimated blood loss (EBL) during cesarean delivery, but its effect on global coagulation as assessed by TEG, and how this correlates with lowering blood loss, has not been elucidated.

This study will be conducted as a randomized, double-blind, controlled trial with two study arms: control (60 patients); and treatment (60 patients).

Subjects will be pre-medicated with routine pre-cesarean delivery medications including oral sodium citrate 30 mL and intravenous (IV) metoclopramide 10 mg. A peripheral IV and noninvasive hemoglobin monitor will be placed, and baseline labs sent: type and screen, serum hemoglobin, platelet count, fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), and baseline TEG values (r time, k time, alpha angle, and maximum amplitude). Patients will have blood pressure, heart rate, and pulse oximetry measured throughout surgery as per standard of care. Patients will all receive IV lactated Ringers' (LR) solution prior to surgery and throughout surgery, with volume recorded and a goal of less than 2 L unless more IV fluid is clinically indicated. All patients will have a spinal anesthetic as per standard of care, with hyperbaric bupivacaine 12 mg, fentanyl 10 μg, and hydromorphone 100 μg. If the anesthetic plan is altered (combined spinal-epidural, general anesthesia conversion, general anesthesia planned), indications and medication doses used will be noted for analysis.

Immediately following induction of anesthesia and prior to skin incision, infusion of study solution will be initiated.

Study solutions will consist of:

1. Control group: 100 mL 0.9% normal saline (NS).
2. Treatment group: 100 mL 0.9% NS containing 1g tranexamic acid (TA). Study solution will be infused via an infusion pump over 10 minutes. Blood loss will be measured by visual estimate and weight of surgical sponges. Noninvasive hemoglobin will be measured throughout the study. All routine care lab values will be noted. At minimum, one lab panel will be sent one hour after study solution initiation (hemoglobin, fibrinogen, platelet count, aPTT, PT, and TEG).

Study Overview

• Status: Terminated
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Placebo; Normal Saline; Drug: Tranexamic Acid

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) class I or II
• aged 18-50 years
• singleton vertex pregnancy
• scheduled elective cesarean delivery (with or without prior labor) with a planned pfannenstiel incision

Exclusion Criteria:

• allergy to tranexamic acid
• history of inherited or acquired thrombophilia
• history of deep vein thrombosis or pulmonary embolism, or use of anticoagulant medication.
• preeclampsia, hemolysis, elevated liver enzymes, low platelet syndrome
• seizure disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control, low risk PPH; Patients at lower risk for postpartum hemorrhage during cesarean delivery, to receive standard of care NOT including tranexamic acid.	Drug: Placebo; Normal Saline; 0.9% Normal Saline
Experimental: Treated, low risk PPH; Patients at lower risk for postpartum hemorrhage during cesarean delivery, to receive standard of care AND tranexamic acid.	Drug: Tranexamic Acid; 1 gram IV over 10 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TEG Value- Thromboelastography R-time, Control and Treated Groups	Blood samples will be collected for evaluation one our after initiation of the study infusion. Whole blood samples are tested in a point-of-care thromboelastography machine and R time, or time to initiation of clot formation, is measured in minutes.	one hour after initiation of study infusion
Intraoperative Blood Loss	Blood loss will be measured using the following methods: visual estimate of blood in the suction canister; weight of surgical sponges; postoperative hemoglobin values	during surgery in the operating room
Delayed Complications at the 6-Week Postpartum Visit With the Obstetrician.	The electronic patient record from each patients' 6-week postpartum visit will be reviewed for the following: delayed bleeding complications, defined as obstetric bleeding requiring surgical intervention, blood transfusion, or both.; thrombotic complications including: venous thrombus seen on ultrasound, thromboembolic event	6 weeks postpartum

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): February 21, 2020

Study Registration Dates

• First Submitted: December 22, 2013
• First Submitted That Met QC Criteria: December 31, 2013
• First Posted (Estimate): January 1, 2014

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 2, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: tranexamic acid; postpartum hemorrhage; coagulation; thromboelastography; estimated blood loss
• 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: 2013P002452