Determination of the Minimal Concentration of Antifibrinolytics Required to Inhibit t-PA-activated Fibrinolysis

Congenital Heart Disease Clinical Trial

Official title:

Determination of the Minimal Concentration of Antifibrinolytics Required to Inhibit t-PA-activated Fibrinolysis Using an in Vitro Experimental Model of Fibrinolysis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352675
• Other study ID #: P00016186
• Status: Completed
• Phase: N/A
• First received: January 26, 2015
• Last updated: July 28, 2017
• Start date: April 2015
• Est. completion date: March 2016

Study information

• Verified date: July 2017
• Source: Boston Children’s Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 12 Months

Eligibility

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

Related Conditions & MeSH terms

• Congenital Heart Disease
• Fibrinolysis
• Heart Diseases
• Rotational Thromboelastometry

Intervention

Other:
• Intraoperative Blood Sample
Blood sample will be run using rotational thromboelastometry to determine the minimal concentration of TXA and EACA need to inhibit fibrinolysis

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children’s Hospital

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. Review. — View 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. — View Citation

Eaton MP. Antifibrinolytic therapy in surgery for congenital heart disease. Anesth Analg. 2008 Apr;106(4):1087-100. doi: 10.1213/ane.0b013e3181679555. Review. — View 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):760-2. doi: 10.1213/ANE.0b013e3182a22278. — View 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. Review. — View 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. — View Citation

Miller BE, Mochizuki T, Levy JH, Bailey JM, Tosone SR, Tam VK, Kanter KR. Predicting and treating coagulopathies after cardiopulmonary bypass in children. Anesth Analg. 1997 Dec;85(6):1196-202. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of antifibrinolytics associated with a complete inhibition of t-PA activated fibrinolysis confirmed by EXTEM test and the Star-TEM test.		One Year