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

NCT02352675 | Completed

• 1 other identifier: P00016186
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Heart Disease; Fibrinolysis; Rotational Thromboelastometry

Outcome Measures

Primary Outcomes (1)

• Concentration of antifibrinolytics associated with a complete inhibition of t-PA activated fibrinolysis confirmed by EXTEM test and the Star-TEM test.

  One Year

Study Arms (2)

Congenital Heart Disease

Infants with congenital heart disease (CHD) who are scheduled to undergo an elective cardiac catheterization lab procedure at Boston Children's Hospital

Other: Intraoperative Blood Sample

Non Congenital Heart Disease

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.

Other: Intraoperative Blood Sample

Interventions

Intraoperative Blood Sample OTHER

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

Congenital Heart Disease; Non Congenital Heart Disease

Eligibility Criteria

• Age: 2 Months - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (9)

• 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. doi: 10.1097/00000539-199712000-00003.

  PMID: 9390579 BACKGROUND

• 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.

  PMID: 21118327 BACKGROUND

• 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.

  PMID: 20117944 BACKGROUND

• Eaton MP. Antifibrinolytic therapy in surgery for congenital heart disease. Anesth Analg. 2008 Apr;106(4):1087-100. doi: 10.1213/ane.0b013e3181679555.

  PMID: 18349177 BACKGROUND

• 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.

  PMID: 22531271 BACKGROUND

• 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.

  PMID: 24057950 BACKGROUND

• 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.

  PMID: 21497106 BACKGROUND

• 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.

  PMID: 23176206 BACKGROUND

• 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.

  PMID: 24646494 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

The doctor will obtain one 13.6 mL blood sample from the arterial catheter or intravenous catheter at the beginning of the procedure after the patient has been anesthetized.

MeSH Terms

Conditions

Heart Defects, Congenital

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• David Faraoni, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiac Anesthesiologist

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: February 2, 2015
• Study Start: April 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: August 1, 2017

Record last verified: 2017-07

Locations

US (1)