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

Pediatric Cardiac Surgery Clinical Trial

— TXAEACA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02656472
• Other study ID #: K5900283
• Status: Completed
• Phase: Phase 4
• First received: December 29, 2015
• Last updated: April 18, 2017
• Start date: February 2016
• Est. completion date: April 2017

Study information

• Verified date: April 2017
• Source: Advocate Health Care
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 activation3 and activation of inflammatory cytokines, especially IL-1 IL-64, IL-8 and 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 CBP 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Complication of Extracorporeal Circulation
• Pediatric Cardiac Surgery

Intervention

Drug:
• Tranexamic acid
TXA Loading dose: 31 mg/kg diluted to 2 ml/kg NS (in syringe) 31 x _______kg = _______ mg TXA (max: 930mg) 2 x _______ kg = _______ ml NS (max: 60 ml) TXA infusion: 14 mg/kg hour = 1 ml/kg/hour (6 hour bag) (Max rate of infusion = 30ml/hr) 14 x ______ kg = _____mg x 6 = ______ mg TXA (max: 2,520mg) 1 x ______ kg = _______ml x 6 = ______ ml NS (max: 180ml) TXA second bolus in 1 ml/kg NS < 16 kg: TXA 45 mg in 1 ml/kg NS = _______ml NS 16-30 kg: TXA 90 mg in 1 ml/kg NS = _______ml NS > 30 kg: TXA 120 mg 1 ml/kg NS = _______ml NS (max 30ml)
• Epsilon Aminocaproic Acid
Aminocaproic acid Loading dose: 75 mg/kg diluted to 2 ml/kg NS 75 x _______kg = _______ mg EACA (max: 2,250mg) 2x _______ kg = _______ ml NS (max 60ml) Aminocaproic acid infusion: 75 mg/kg hour = 1 ml/kg/hour (6 hour bag) 75 x ______ kg = _____mg x 6 = ______ mg EACA (max: 13,500 mg) 1 x ______ kg = _______ml x 6 = ______ ml NS (max: 180ml) Aminocaproic acid second bolus: 75 mg/kg in 1ml/kg NS 75 x _______kg = _______ mg EACA (max: 2,250mg) 1 x _______ kg = _______ ml NS (max 30 ml)

Locations

Country	Name	City	State
United States	Advocate Childrens Hospital	Oak Lawn	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Andrew VanBergen, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of pro inflammatory markers/cytokines by comparing Area under curve of cytokine production	Area under the curve (AUC) of cytokine production. Markers to be analyzed include (part of single cytokine multiplex assay); GM-CSF; IFN gamma; IL-1beta; IL-2; IL-4; IL-6; IL-8; IL-10; IL-12(p70); MCP-1; TNF-alpha	upto 24 hours post surgery
Primary	time to net negative fluid balance	Compare time taken for patient to have net negative fluid balance during first 2 weeks post surgery	assessed at 2 weeks
Primary	time of chest tube removal	compare time of chest tube removal in hours in the two groups	time to chest tube removal or death whichever is earlier, assessed at 1 month
Secondary	Chest tube output in first 48 hours		assessed at 48 hours
Secondary	Compare the volume of blood product replacement needed in first 48 hours of surgery (including blood products used in OR), in each study arm	reported in milliliters (ml) for each patient	48 hours after surgery
Secondary	Comparison of antifibrinolytic effect of TXA vs EACA using routine lab tests	TEG, Fibrinogen, D-Dimer, CBC, CMP	baseline and 24 hours
Secondary	ICU length of stay and Hospital length of stay	evaluated through study completion	compare length of stay in days of patients in each study arm, at an average of 2 months