Blood Loss and Transfusion Requirement in Infants Treated With Tranexamic Acid

Study Description

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Brief Summary:

The primary objective of this study is to investigate whether tranexamic acid (TXA) reduces perioperative blood loss and transfusion requirement in infants undergoing craniosynostosis surgery.

Condition or disease	Intervention/treatment	Phase
Craniosynostoses	Drug: Tranexamic Acid; Drug: Saline Placebo	Phase 3

Detailed Description:

Blood loss during pediatric craniosynostosis surgery can be significant and this may be exacerbated by a dilutional coagulopathy. Multimodal blood conservation strategies may limit allogeneic transfusions, although RCTs are few and limited. It is essential to investigate these techniques to determine their potential to reduce allogeneic blood transfusions and their associated cost and morbidity.

Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively inhibits the lysine binding sites of plasminogen, plasmin, and tissue plasminogen activator. The result is inhibition of fibrinolysis and clot degradation.

Recent studies in adults undergoing cardiac surgery demonstrated that people with different genotypes for the plasminogen activator inhibitor-1 (PAI-1) gene may have varying degrees of bleeding. PAI-1 inhibits the transformation of plasminogen to plasmin thereby decreasing plasmin-induced fibrinolysis. Thus, PAI-1 promotes clot stability and the PAI-1 polymorphism will affect the degree of bleeding and response to TXA during craniosynostosis surgery.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	90 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Blood Loss and Transfusion Requirement in Infants Treated With Tranexamic Acid Undergoing Craniosynostosis Reconstruction: A Randomized Placebo-Controlled Double Blind Study of Low and High Dose Therapy
Study Start Date :	January 2010
Estimated Primary Completion Date :	January 2015
Estimated Study Completion Date :	January 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Low Dose; TXA 10mg/kg bolus before incision and 5 mg/kg infusion until skin closure	Drug: Tranexamic Acid; 10 mg/kg bolus with a 5 mg/kg/h infusion
Experimental: High Dose; TXA 100 mg/kg bolus before incision and 10 mg/kg infusion until skin closure	Drug: Tranexamic Acid; 100 mg/kg bolus with a 10 mg/kg/h infusion
Placebo Comparator: Placebo; Normal saline 10 ml before skin incision and infusion according to weight until skin closure	Drug: Saline Placebo

Outcome Measures

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Primary Outcome Measures :

1. Blood Loss [ Time Frame: Prior and Post Surgery ]
   Blood loss will be carefully measured in sponges, suction cannisters, cell saver systems, and in the plastic pockets of surgical drapes.

Secondary Outcome Measures :

1. Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphism - Samples [ Time Frame: Sample will be drawn immediately after induction and prior to administration of study drug ]
   PAI-1 promotes clot stability and the PAI-1 polymorphism will affect the degree of bleeding and response to TXA during craniosynostosis surgery
2. Thromboelastography (TEG)Sample [ Time Frame: Baseline, immediately after bolus dose of TXA is infused ]
   TEG monitors coagulation of blood samples in vitro to produce a complete picture of clot formation, strength and dissolution (i.e. fibrinolysis)

Eligibility Criteria

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Ages Eligible for Study:	2 Months to 2 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Infants aged 2 months to 2 years undergoing anterior cranial vault reconstruction

Exclusion Criteria:

• Known bleeding disorder as this may increase the risk of bleeding
• Current antifibrinolytic therapy as these patients may bleed less
• Patient or family history of thromboembolic disease as there may be potential risk of thrombosis
• Use of NSAIDS within 5 days of surgery as this may increase the risk of bleeding
• Known allergy to TXA
• History of renal insufficiency as TXA is renally excreted
• Acquired colour vision defects as one of the first signs of long term TXA toxicity is colour vision disturbance.

Contacts and Locations

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Contacts

Contact: Tara Der, MD	416-813-7654 ext 2405	tara.der@sickkids.ca
Contact: Carolyne Pehora, RN	416-813-7654 ext 2406	carolyne.pehora@sickkids.ca

Locations

Canada, Ontario
The Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada
Principal Investigator: Tara Der, MD
Sub-Investigator: Christian Zaarour, MD
Sub-Investigator: Mark Crawford, MD
Sub-Investigator: Guy Petroz, MD

Sponsors and Collaborators

The Hospital for Sick Children

Investigators

Principal Investigator:	Tara Der, MD	The Hospital for Sick Children

More Information

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Responsible Party:	Tara Der, Staff Anesthesiologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT01094977 History of Changes
Other Study ID Numbers:	1000013836
First Posted:	March 29, 2010
Last Update Posted:	August 28, 2013
Last Verified:	August 2013

Keywords provided by Tara Der, The Hospital for Sick Children:

Blood Loss and Transfusion; Craniosynostoses; Tranexamic Acid; Children

Additional relevant MeSH terms:

Craniosynostoses; Hemorrhage; Pathologic Processes; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities	Musculoskeletal Abnormalities; Congenital Abnormalities; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants