Blood Loss and Transfusion Requirement in Infants Treated With Tranexamic Acid

Phase 3

Suspended

• Conditions: Craniosynostoses
• Interventions: Drug: Saline Placebo; Drug: Tranexamic Acid

• Registration Number: NCT01094977
• Lead Sponsor: The Hospital for Sick Children

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.

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 Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-03-23
• Study First Submitted QC: 2010-03-26
• Study First Posted: 2010-03-29
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-11
• Last Update Posted: 2019-07-15
• Primary Completion: 2020-01
• Study Completion: 2020-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 90

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Saline Placebo	Normal saline 10 ml before skin incision and infusion according to weight until skin closure
High Dose	Tranexamic Acid	TXA 100 mg/kg bolus before incision and 10 mg/kg infusion until skin closure
Low Dose	Tranexamic Acid	TXA 10mg/kg bolus before incision and 5 mg/kg infusion until skin closure

Primary Outcome Measures

Name	Time	Method
Blood Loss	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

Name	Time	Method
Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphism - Samples	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
Thromboelastography (TEG)Sample	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)

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada