Clinical trial NCT02352675: Determination of the Minimal Concentration of Antifibrinolytics Required to Inhibit t-PA-activated Fibrinolysis
Official title: Determination of the Minimal Concentration of Antifibrinolytics Required to Inhibit t-PA-activated Fibrinolysis Using an in Vitro Experimental Model of Fibrinolysis.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Fibrinolysis
Rotational Thromboelastometry
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 40
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a prospective in vitro study being performed on whole blood obtained from two groups of infants. The first group will include infants with congenital heart disease (CHD) who are scheduled to undergo an elective cardiac catheterization lab procedure at Boston Children's Hospital. The second group will include infants who do not have congenital heart disease (No-CHD) and are scheduled to undergo a non-cardiac surgery (such as craniofacial surgery, neurosurgery, or orthopedic surgery) in the operating room at Boston Children's Hospital.

Brief summary: Lysine analogs, like tranexamic acid (TXA) or epsilon aminocaproic acid (EACA), are antifibrinolytic agents routinely administered in children undergoing different surgeries associated with a high bleeding risk (e.g. cardiac, craniofacial, and orthopedic surgeries). Although there is a growing literature regarding the pharmacokinetic characteristics of these drugs in children, the plasmatic concentration required to completely inhibit fibrinolysis remains to be determined. In this in vitro study, the investigators will use an experimental model of fibrinolysis designed for rotational thromboelastometry (ROTEM®) to determine the minimal concentration inhibiting fibrinolysis for both TXA and EACA. In addition, this study will be used to create and validate a new experimental assay to measure fibrinolysis and the effect of antifibrinolytic agents.


Eligibility criteria: Inclusion Criteria:

* infants between 2 months of age and equal to or less than 12 months of age
* weigh over 5.0 kg
* either have CHD and are scheduled to undergo an elective cardiac catheterization lab procedure or do not have CHD and are scheduled to undergo a non-cardiac surgery (such as craniofacial surgery, neurosurgery, or orthopedic surgery) in the operating room

Exclusion Criteria:

* undergoing an emergent procedure,
* child in a moribund condition (American Society of Anesthesiology (ASA 5)
* children with a hematological and/or oncological disease
* Jehovah witnesses
* children with preoperative coagulopathy, defined as a platelet count \< 100,000/μL, fibrinogen level \< 100 mg/dL, prothrombin time (PT) and activated partial thromboplastin time (PTT) \> 1.5 normal range

Primary outcomes:
measure: Concentration of antifibrinolytics associated with a complete inhibition of t-PA activated fibrinolysis confirmed by EXTEM test and the Star-TEM test.
timeFrame: One Year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: David Faraoni, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Arnold P. Treatment and monitoring of coagulation abnormalities in children undergoing heart surgery. Paediatr Anaesth. 2011 May;21(5):494-503. doi: 10.1111/j.1460-9592.2010.03461.x. Epub 2010 Dec 1.
citation: Ngaage DL, Bland JM. Lessons from aprotinin: is the routine use and inconsistent dosing of tranexamic acid prudent? Meta-analysis of randomised and large matched observational studies. Eur J Cardiothorac Surg. 2010 Jun;37(6):1375-83. doi: 10.1016/j.ejcts.2009.11.055. Epub 2010 Feb 1.
citation: Eaton MP. Antifibrinolytic therapy in surgery for congenital heart disease. Anesth Analg. 2008 Apr;106(4):1087-100. doi: 10.1213/ane.0b013e3181679555.
citation: Faraoni D, Willems A, Melot C, De Hert S, Van der Linden P. Efficacy of tranexamic acid in paediatric cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2012 Nov;42(5):781-6. doi: 10.1093/ejcts/ezs127. Epub 2012 Apr 24.
citation: Faraoni D, Goobie SM. New insights about the use of tranexamic acid in children undergoing cardiac surgery: from pharmacokinetics to pharmacodynamics. Anesth Analg. 2013 Oct;117(4):760-762. doi: 10.1213/ANE.0b013e3182a22278. No abstract available.
citation: Faraoni D. Safety of tranexamic acid in pediatric cardiac surgery: what we do not know. Eur J Cardiothorac Surg. 2011 Dec;40(6):1550-1; author reply 1551-2. doi: 10.1016/j.ejcts.2011.03.009. Epub 2011 Apr 14. No abstract available.
citation: Raza I, Davenport R, Rourke C, Platton S, Manson J, Spoors C, Khan S, De'Ath HD, Allard S, Hart DP, Pasi KJ, Hunt BJ, Stanworth S, MacCallum PK, Brohi K. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost. 2013 Feb;11(2):307-14. doi: 10.1111/jth.12078.
citation: Dekker SE, Viersen VA, Duvekot A, de Jong M, van den Brom CE, van de Ven PM, Schober P, Boer C. Lysis onset time as diagnostic rotational thromboelastometry parameter for fast detection of hyperfibrinolysis. Anesthesiology. 2014 Jul;121(1):89-97. doi: 10.1097/ALN.0000000000000229.