Blood Loss and Transfusion Requirement in Infants Treated With Tranexamic Acid

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

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.

Study Overview

• Status: Suspended
• Conditions: Craniosynostoses
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Tranexamic Acid; Drug: Saline Placebo

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 Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / 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; Drug: Tranexamic Acid; 100 mg/kg bolus with a 10 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; 10 mg/kg bolus with a 5 mg/kg/h infusion; 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

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: March 23, 2010
• First Submitted That Met QC Criteria: March 26, 2010
• First Posted (Estimate): March 29, 2010

Study Record Updates

• Last Update Posted (Actual): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Children; Tranexamic Acid; Blood Loss and Transfusion; Craniosynostoses
• Additional Relevant MeSH Terms: Pathologic Processes; Congenital Abnormalities; Musculoskeletal Diseases; Bone Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Bone Diseases, Developmental; Dysostoses; Synostosis; Hemorrhage; Craniosynostoses; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 1000013836