Prevention of Intraoperative Bleeding and Postoperative Swelling in Orthognathic Surgery Through the Use of Tranexamic Acid (TXA2014-15)

Prevention of Bleeding and Edema in Bimaxillary Orthognathic Surgery; the Effectiveness of Tranexamic Acid on Intraoperative Bleeding and Postoperative Swelling in Orthognathic Surgery.

Purpose of the study:

• To evaluate the effect of tranexamic acid (TXA) of intraoperative blood loss in patients subjected to bi-maxillary orthognathic surgery
• To evaluate the potential effect of TXA on fibrin structure
• To evaluate the potential effect of TXA of binding of plasminogen to fibrin
• To evaluate the potential effect of TXA on postoperative edema formation.

Hypothesis:

H0: Intraoperative bleeding cannot be significantly reduced by preoperative administration of tranexamic acid

H0,1: Postoperative edema cannot be significantly reduced by preoperative administration of tranexamic acid

Study Overview

• Status: Completed
• Conditions: Postoperative Edema; Intraoperative Bleeding
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Saline

Detailed Description

The study population consists of patients referred to simultaneous mandibular and maxillary osteotomy at the Department of Oral and Maxillofacial Surgery, Hospital of South West Denmark in 2014.

Hundred patients (50 men and 50 women) will be enrolled in the study. Reportedly, the mean intraoperative blood loss in the placebo group is expected to be 436 ml with a standard deviation of 208 ml. The difference in blood loss between the TXA-group and the placebo group to be detected is 100 ml. The dropout frequency is estimated to 10%. To fulfil these assumptions a minimum of 40 patients should be included in each group to reach a power of 0.8 and an alpha of 0.05. In order to accommodate an even gender distribution a block randomization is performed resulting in the randomization of 100 patients.

The patients will be randomized to receive blindly either 10 ml tranexamic acid (100 mg/ml) (Pfizer, Ballerup, Denmark) or 10 ml saline (9mg/ml) preoperatively. Intraoperative blood loss will be determined by deducting the total volume of irrigation fluids from the volume of the contents of the surgical suction device. Postoperative edema formation will be determined by 3D surface scanning and volumetric analysis will be carried out in the "Landmarker" software.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Hospital of South West Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be 18 years or older
• Patients must be eligible for elective bi-maxillary orthognathic surgery
• No severe reduction of kidney function
• No known medical conditions
• Signed informed consent

Exclusion Criteria:

• Hypersensitivity to tranexamic acid
• A medical history of acute venous thrombosis and/or arterial thrombosis
• The presence of fibrinolytic conditions as a result of disseminated intravascular coagulation, with the exception of a predominant activation of the fibrinolytic system with acute severe bleeding.
• Severe kidney deficiency
• Cramps in the medical history
• Intake of Omega-3 fatty acids, Gingko Biloba, ginger and garlic supplements within 3 months of surgery.
• Pregnancy (female participants will be tested on the day of surgery)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tranexamic acid; The active comparator consists of an intravenously administered bolus injection of 10ml of 100mg/ml tranexamic (1g in total) given as a single dose, after the onset of anesthesia, prior to surgery.	Drug: Tranexamic Acid; Active group: Undergoes elective bi-maxillary orthognathic surgery consisting of a (un)/segmented LeFort I osteotomy combined with a bilateral sagittal split osteotomy, under the influence of 10ml tranexamic acid (100mg/ml) administered iv. prior to the onset of the surgical procedure.; Other Names: Tranexamsyre "Pfizer", D.SP.NR.: 22646, ATC code: B 02 AA 02
Placebo Comparator: Saline; The placebo consists of an intravenously administered bolus injection of 10 ml of 9mg/ml sodium chloride given as a single dose after the onset of anesthesia, prior to surgery.	Drug: Saline; Placebo group: Undergoes elective bi-maxillary orthognathic surgery consisting of a (un)/segmented LeFort I osteotomy combined with a bilateral sagittal split osteotomy, under the influence of 10ml sodium chloride (9mg/ml) administered iv. prior to the onset of the surgical procedure.; Other Names: Natriumklorid "B. Braun", D.SP.NR.: 6856, ATC code: V 07 AB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intra-operative bleeding volume (ml)	Within 10 minutes after ended surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemostatic profile	Changes in the hemostatic profile measured through thrombelastography, thrombin generation test and fibrin structure analysis.	Baseline, 5.5 hours, 48 hours and 4 months postoperatively
Change in inflammatory profile	Changes in the inflammatory profile are investigated through measures of surface induced activation, inflammation and plasminogen binding.	Baseline, 5.5 hours, 48 hours and 4 months postoperatively
Postoperative edema formation	The degree of postoperative swelling in connection with TXA /or not, is determined by non-invasive 3D face scans and quantified using the "Landmarker" software. Scans are carried out along with the 3rd and 4th blood samples, 48 hours and 4 months postoperatively.	48 hours and 4 months postoperatively

Collaborators and Investigators

• Sponsor: Hospital of South West Jutland
• Collaborators: University of Copenhagen; Vestjydsk Ortopædisk Fond
• Investigators: Principal Investigator: Jesper J Olsen, DDS, Hospital of South West Jutland

Publications and helpful links

General Publications

• Song G, Yang P, Hu J, Zhu S, Li Y, Wang Q. The effect of tranexamic acid on blood loss in orthognathic surgery: a meta-analysis of randomized controlled trials. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 May;115(5):595-600. doi: 10.1016/j.oooo.2012.09.085. Epub 2012 Dec 20.

Study record dates

Study Major Dates

• Study Start: August 19, 2014
• Primary Completion (Actual): September 26, 2016
• Study Completion (Actual): September 26, 2016

Study Registration Dates

• First Submitted: August 28, 2014
• First Submitted That Met QC Criteria: August 28, 2014
• First Posted (Estimate): September 1, 2014

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Intraoperative Complications; Hemorrhage; Blood Loss, Surgical; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 2013-005473-52