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

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ClinicalTrials.gov Identifier: NCT02656472
Recruitment Status : Completed
First Posted : January 15, 2016
Last Update Posted : April 20, 2017
Sponsor:
Information provided by (Responsible Party):
Andrew VanBergen, MD, Advocate Health Care

Brief 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.

Condition or disease Intervention/treatment Phase
Pediatric Cardiac Surgery Complication of Extracorporeal Circulation Drug: Tranexamic acid Drug: Epsilon Aminocaproic Acid Phase 4

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 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: A Pilot Study Comparing Anti-Inflammatory Effects Of Tranexamic Acid Versus Epsilon Aminocaproic Acid In Pediatric Congenital Heart Surgery
Actual Study Start Date : February 2016
Actual Primary Completion Date : April 2017
Actual Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

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 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)

Other Name: 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

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)

Other Name: EACA




Primary Outcome Measures :
  1. Comparison of pro inflammatory markers/cytokines by comparing Area under curve of cytokine production [ Time Frame: upto 24 hours post surgery ]

    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

  2. time to net negative fluid balance [ Time Frame: assessed at 2 weeks ]
    Compare time taken for patient to have net negative fluid balance during first 2 weeks post surgery

  3. time of chest tube removal [ Time Frame: time to chest tube removal or death whichever is earlier, assessed at 1 month ]
    compare time of chest tube removal in hours in the two groups


Secondary Outcome Measures :
  1. Chest tube output in first 48 hours [ Time Frame: assessed at 48 hours ]
  2. Compare the volume of blood product replacement needed in first 48 hours of surgery (including blood products used in OR), in each study arm [ Time Frame: 48 hours after surgery ]
    reported in milliliters (ml) for each patient

  3. Comparison of antifibrinolytic effect of TXA vs EACA using routine lab tests [ Time Frame: baseline and 24 hours ]
    TEG, Fibrinogen, D-Dimer, CBC, CMP

  4. ICU length of stay and Hospital length of stay [ Time Frame: compare length of stay in days of patients in each study arm, at an average of 2 months ]
    evaluated through study completion



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02656472


Locations
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United States, Illinois
Advocate Childrens Hospital
Oak Lawn, Illinois, United States, 60453
Sponsors and Collaborators
Andrew VanBergen, MD
Investigators
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Principal Investigator: Andrew VanBergen, M.D. Director, Section of Pediatric Cardiac Critical Care

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Responsible Party: Andrew VanBergen, MD, Director Pediatric Cardiac Critical Care, Advocate Health Care
ClinicalTrials.gov Identifier: NCT02656472     History of Changes
Other Study ID Numbers: K5900283
First Posted: January 15, 2016    Key Record Dates
Last Update Posted: April 20, 2017
Last Verified: April 2017

Keywords provided by Andrew VanBergen, MD, Advocate Health Care:
Pediatric Cardiac surgery
Inflammatory response
Tranexamic acid
Epsilon Aminocaproic Acid

Additional relevant MeSH terms:
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Tranexamic Acid
Aminocaproic Acid
Anti-Inflammatory Agents
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants