Tranexamic Acid for Craniofacial Surgery

Tranexamic Acid for the Reduction of Allogeneic Blood Exposure in Infants and Children Having Craniofacial Surgery

This is a randomized, blinded, prospective study that will investigate the potential benefit of tranexamic acid to reduce the intraoperative bleeding and blood transfusions in pediatric patients undergoing craniofacial surgeries.

Study Overview

• Status: Terminated
• Conditions: Bleeding; Craniosynostosis
• Intervention / Treatment: Drug: Tranexamic acid; Drug: saline

Detailed Description

Surgical procedures for the correction of craniofacial deformities result in unavoidable and significant blood loss in small children and infants. Patients may experience blood losses that exceed one to two blood volumes. In an effort to reduce our transfusion requirements, we have introduced tranexamic acid into our practice. However, the benefit of tranexamic acid in pediatric craniofacial surgery has not yet been reported. We hypothesize that the intraoperative use of tranexamic acid in pediatric patients presenting for craniofacial reconstructions will reduce blood loss and allogeneic transfusion requirements.

This is a randomized, blinded, prospective study that will investigate the potential benefit of tranexamic acid to reduce the intraoperative bleeding and blood transfusions in pediatric patients undergoing craniofacial surgeries. An initial dose of 100 mg/kg tranexamic acid (Cyclokapron 100mg/ml) or an equal volume of a placebo will be administered over 15 minutes after the induction of anesthesia and before the skin incision. A maintenance infusion of 10 mg/kg/hr of tranexamic acid or equal volume of a placebo will be started upon completion of the initial dose and will be continued until skin closure. The primary outcome will include the reduction in the total volume of allogeneic erythrocytes.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • The Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The inclusion of the patients will depend on the following criteria:

1. All pediatric patients scheduled for primary or secondary repair of craniosynostosis with a frontal orbital advancement, or cranial vault reconstruction.
2. Patients will be between the ages of 6 months and 18 years old.
3. They will be > than 5 kg.
4. All subjects being evaluated in the Craniofacial Clinic for primary or secondary repair of craniosynostosis will potentially be included in the study. Prior to inclusion in the study potential participants will be screened by history and laboratory data. The laboratory data will include a complete blood count, PT, PTT, type and cross, factor V leiden, anticardiolipin antibody, and lupus anticoagulant. The history will be obtained from the parents or current care takers. The medical records may be reviewed if there is a need for clarification.

Exclusion Criteria:

Patients that will be excluded from the study include the following:

1. Familial or personal coagulopathy risk-factor V leiden, anticardiolipin antibody, and lupus anticoagulant
2. Abnormal PT, PTT, Platelet count. or closing time. All patients presenting for craniofacial surgery have preoperative blood work performed which includes a type and screen, HCT, PLT, PT, PTT, and closing time. Patients who have abnormalities detected in their coagulation profile proceed on to a complete hematologic evaluation that includes an evaluation for Von Willebrand's Disease.
3. History of thrombotic episodes in the patient
4. Renal failure or hepatic failure.
5. Infants less than 5 kg
6. Age < 6 months or > 18 years old

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic acid; Tranexamic acid (100 mg/kg load, 10 mg/kg/hr) intravenous	Drug: Tranexamic acid; 100 mg/kg load, then 10 mg/kg/hr
Placebo Comparator: Placebo; Saline was administered intravenously	Drug: saline; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Volume (ml/kg) of Allogeneic Blood Exposure.	This is the blood administered during surgery. The blood comes form the blood bank. It is not cell salvage blood. The volume was normalized by weight.	intraoperative and postoperative (24 hr)
Number of Patients That Remained Transfusion Free		24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure).	(baseline, after osteotomies, and immediately after procedure)
Platelets	baseline, after osteotomies, immediately after surgery

Collaborators and Investigators

• Sponsor: University of Pittsburgh

Publications and helpful links

General Publications

• Sethna NF, Zurakowski D, Brustowicz RM, Bacsik J, Sullivan LJ, Shapiro F. Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology. 2005 Apr;102(4):727-32. doi: 10.1097/00000542-200504000-00006.
• Neilipovitz DT, Murto K, Hall L, Barrowman NJ, Splinter WM. A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. Anesth Analg. 2001 Jul;93(1):82-7. doi: 10.1097/00000539-200107000-00018.
• Henry DA, Moxey AJ, Carless PA, O'Connell D, McClelland B, Henderson KM, Sly K, Laupacis A, Fergusson D. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2001;(1):CD001886. doi: 10.1002/14651858.CD001886.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: July 23, 2008
• First Submitted That Met QC Criteria: July 24, 2008
• First Posted (Estimate): July 25, 2008

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: antifibrinolytic, tranexamic acid
• Additional Relevant MeSH Terms: Congenital Abnormalities; Musculoskeletal Diseases; Bone Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Bone Diseases, Developmental; Dysostoses; Synostosis; Craniosynostoses; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: PRO07120134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We stopped the study early because emerging data came out that demonstrated benefit with significantly lower doses than our study. We were compelled to stop enrolling.