Blood Loss and Transfusion Requirement in Infants Treated With Tranexamic Acid

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Craniosynostoses

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Tranexamic Acid
* Drug: Saline Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>TXA 10mg/kg bolus before incision and 5 mg/kg infusion until skin closure | Drug: Tranexamic Acid<br>* 10 mg/kg bolus with a 5 mg/kg/h infusion<br>|
| Experimental: High Dose<br>TXA 100 mg/kg bolus before incision and 10 mg/kg infusion until skin closure | Drug: Tranexamic Acid<br>* 100 mg/kg bolus with a 10 mg/kg/h infusion<br>|
| Placebo Comparator: Placebo<br>Normal saline 10 ml before skin incision and infusion according to weight until skin closure | Drug: Saline Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Loss | Blood loss will be carefully measured in sponges, suction cannisters, cell saver systems, and in the plastic pockets of surgical drapes. | Prior and Post Surgery | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Loss and Transfusion, Craniosynostoses, Tranexamic Acid, Children