Clinical trial NCT02656472: A Pilot Study Comparing Anti-Inflammatory Effects Of TXA Versus EACA In Pediatric Congenital Heart Surgery
Official title: A Pilot Study Comparing Anti-Inflammatory Effects Of Tranexamic Acid Versus Epsilon Aminocaproic Acid In Pediatric Congenital Heart Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pediatric Cardiac Surgery
Complication of Extracorporeal Circulation
Keywords: Pediatric Cardiac surgery
Inflammatory response
Tranexamic acid
Epsilon Aminocaproic Acid
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2016-01-15
Enrollment: 22
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Inflammatory Markers/Cytokines
timeFrame: 24 hours post-surgery
Secondary outcomes:
measure: Chest Tube Output
timeFrame: 48 hours post-surgery
measure: Blood Replacement Volume
timeFrame: 48 hours post-surgery
measure: Platelet Levels
timeFrame: Immediately post-surgery and 24 hours post-surgery
measure: Liver Enzymes
timeFrame: Immediately post-surgery and 24 hours post-surgery
measure: Hemoglobin
timeFrame: Immediately post-surgery and 24 hours post-surgery
measure: Creatinine
timeFrame: Immediately post-surgery and 24 hours post-surgery
measure: Length of Stay
timeFrame: 2 months
Other outcomes:
Locations:
city: Oak Lawn
country: United States
facility: Advocate Childrens Hospital
state: Illinois
Study officials:
affiliation: Director, Section of Pediatric Cardiac Critical Care
name: Andrew VanBergen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: