A Pilot Study Comparing Anti-Inflammatory Effects Of TXA Versus EACA In Pediatric Congenital Heart Surgery (TXAEACA)

A Pilot Study Comparing Anti-Inflammatory Effects Of Tranexamic Acid Versus Epsilon Aminocaproic Acid In Pediatric Congenital Heart Surgery

The purpose of this study is to compare anti-inflammatory effects of two anti-fibrinolytic drugs (Tranexamic acid versus Epsilon-aminocaproic acid) in pediatric patients undergoing pediatric cardiac surgery.

Study Overview

• Status: Completed
• Conditions: Pediatric Cardiac Surgery; Complication of Extracorporeal Circulation
• Intervention / Treatment: Drug: Tranexamic acid; Drug: Epsilon Aminocaproic Acid

Detailed Description

Bleeding under cardiopulmonary bypass (CPB) is one of the most common complications in patients undergoing pediatric cardiac surgery. The inflammatory response produced during and after CPB is a factor that adds significantly to the morbidity after cardiac surgery. A number of factors have been shown to be involved inducing the inflammatory response. These include complement system activation and activation of inflammatory cytokines, especially Interleukin (IL)-1, IL-6, IL-8 and Tumor necrosis factor (TNF) alpha.

Tranexamic Acid (TXA) and Epsilon-Aminocaproic Acid (EACA) are lysine analogues frequently used as anti-fibrinolytic agents in patients undergoing CPB. Many authors have highlighted the role of TXA in reducing blood loss and blood transfusion during and after CPB. Role of EACA and aprotinin in decreasing pro-inflammatory response during and after CPB has been well documented in adult literature. Patients undergoing redo sternotomy have higher inflammatory response as compared to patients undergoing first cardiac surgery. It has also been shown that the TXA can reduce the inflammatory response after CPB by acting directly or indirectly on the inflammatory cytokines.

There are no studies directly comparing the anti-inflammatory properties of EACA and TXA in the pediatric population undergoing CPB. In our institution, EACA is used as the standard of practice to reduce the blood loss during pediatric cardiac surgeries, but the investigators have now started using TXA more recently.

The aim of this study is to compare the anti-inflammatory and anti-fibrinolytic properties of these two anti-fibrinolytic agents in pediatric patients undergoing CPB for cardiac surgery.

Hypothesis: Tranexamic acid (TXA) has better anti-inflammatory profile as compared to €-Amino Caproic Acid (EACA) which may help in reducing blood loss, renal injury, hepatic injury and blood transfusion during and after CPB

Specific Objectives: During redo sternotomy procedures there is significant anti-inflammatory response which occurs and plays a role in increasing amount chest tube output, blood loss, renal injury, hepatic injury and ultimately patient morbidity and/or mortality. The proposed study will help to know if antifibrinolytic agents are beneficial in reducing the anti-inflammatory response produced and which of the two drugs (EACA or TXA), has a better anti-inflammatory profile when used in a similar setting for patients undergoing pediatric cardiothoracic surgery.

Specific Aims:

Evaluate whether TXA or EACA can decrease inflammatory response produced during redo sternotomy procedures in pediatric patients and which drug decreases the injury and/or cardiac dysfunction more as reflected by fluid balances, inotropic support, diuretic requirement, length of ventilator support, length of ICU stay, and length of hospital stay.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing pediatric cardiac surgery, with redo sternotomy needing cardiopulmonary bypass

Exclusion Criteria:

• Patients undergoing Fontan or Glenn procedures
• Allergy to EACA or TXA

• Baseline coagulation profile abnormality * (The coagulation profile will be used as an exclusion criteria, if results available. Occasionally the results of coagulation profile may be unavailable prior to surgery due to a clotted sample. For such patients, as per the current clinical practice, we would not be redrawing the lab solely for a research purpose)

  • Prothrombin time (PT) >50% of High Normal value
  • Partial Thromboplastin Time (PTT) > 50% of High Normal value
  • Platelets < 50,000/mm3
  • International normalized ratio (INR) >2
• Acute or chronic renal failure (creatinine > 2x high normal for age)
• Chronic hepatopathy (any transaminase > 2x high normal for age)
• Use of immunosuppressant drugs (within last 1 month)
• History of seizures (currently on antiepileptic drugs for epilepsy or history of seizure within last 6 months)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tranexamic Acid Arm; TXA arm will include 10 subjects who will receive TXA for duration of surgery.	Drug: Tranexamic acid; TXA Loading dose: 31 mg/kg diluted to 2 ml/kg Normal saline (NS) -in syringe; Other Names: TXA
Active Comparator: Epsilon Aminocaproic Acid Arm; EACA arm will include 10 subjects who will receive EACA for the duration of surgery.	Drug: Epsilon Aminocaproic Acid; Aminocaproic acid Loading dose: 75 mg/kg diluted to 2 ml/kg NS; Other Names: EACA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Markers/Cytokines	Consented patients had research-related blood draws (0.3 ml) at three time points: pre-CPB, post-CBP following protamine administration and 24 hours post-CPB. Average of the values run in duplicate was used for calculations. For samples with values reported as out of range (due to level being below detection), the lowest detectable value was assigned for analysis.	24 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest Tube Output	Chest tube output in ml/kg for the first 48 hours	48 hours post-surgery
Blood Replacement Volume	Compare the volume of blood product replacement needed in first 48 hours of surgery (including blood products used in OR)	48 hours post-surgery
Platelet Levels	Antifibrinolytic effect using platelets levels x 1000/mL	Immediately post-surgery and 24 hours post-surgery
Liver Enzymes	Tests were recorded and compared between the groups to analyze the effect of the antifibrinolytic agent used on the amount of blood loss as well as effect of inflammation on the liver and kidney.	Immediately post-surgery and 24 hours post-surgery
Hemoglobin	Tests were recorded and compared between the groups to analyze the effect of the antifibrinolytic agent used on the amount of blood loss as well as effect of inflammation on the liver and kidney.	Immediately post-surgery and 24 hours post-surgery
Creatinine	Tests were recorded and compared between the groups to analyze the effect of the antifibrinolytic agent used on the amount of blood loss as well as effect of inflammation on the liver and kidney.	Immediately post-surgery and 24 hours post-surgery
Length of Stay	Length of stay in the ICU and overall hospital stay.	2 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Andrew VanBergen, M.D., Director, Section of Pediatric Cardiac Critical Care

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: January 14, 2016
• First Posted (Estimated): January 15, 2016

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Inflammatory response; Tranexamic acid; Epsilon Aminocaproic Acid; Pediatric Cardiac surgery
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antifibrinolytic Agents; Fibrin Modulating Agents; Hemostatics; Coagulants; Tranexamic Acid; Aminocaproic Acid
• Other Study ID Numbers: K5900283