Testing of the Drug Tranexamic Acids as Prophylaxis of Bleeding in Benign Surgical Removal of the Uterus

Study Overview
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Brief Summary
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In Denmark, 4400 women annually undergo hysterectomy on benign background (surgical removal of the uterus). 10% of these women experience bleeding complications. The drug Tranexamic Acid (Cyklokapron) has showed significant reduction of bleeding in relation to other types of surgery. The hypothesis of this study is that Tranexamic Acid could also reduce the operative bleeding associated with benign hysterectomy. The study will be carried out as a randomized, placebo-controlled national multicenter trial

Detailed Description
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In Denmark, there are approximately 4400 elective benign hysterectomies annually. In about 10% of these there will occur a per- or postoperative bleeding complications with increased hospital stay, reoperations and prolonged sick leave as a result. The pharmaceutical product 'Tranexamic acid' has proved to be effective in reducing blood loss in other forms of surgery, in trauma patients, and in relation to certain medical conditions. The hypothesis of the proposed study is that Tranexamic acid could also reduce the operative bleeding associated with hysterectomy on benign indications. Based on the literature and previous studies, the objective of the trial is an average bleeding reduction of 25%. The clinical trial will be conducted as a randomized, placebo-controlled, double blind multicenter trial in gynecological departments several places in Denmark: Nordsjællands Hospital, Rigshospitalet, Odense University Hospital and Aarhus University Hospital - Skejby. The subjects will be recruited in outpatient clinics of the gynecological departments. During the study there will be an ongoing monitoring by external partner. The experiment is approved by all relevant bodies. The total period of time in which the trial is planned to last is one year commencing 01.02.3013 and ending 28.02.2014. All together the trial will include 314 participants determined by presumed bleeding reduction, the average bleeding on hysterectomy and type 1 error of 0.05 and type 2 error of 0.20. Randomization will be conducted electronically and both clinician, patient and data collector we will be blinded. Data for the study will partly be collected through registrations to the already well established and well functioning Danish Hysterectomy and Hysteroscopy Database. Data used in relation to the study will be validated by examining the manual records in conjunction with data extraction. The results will be analyzed by univariate and multivariate analyzes and static regression analyzes. All final results from the study will be sought published in recognized international journals. Regarding ethical aspects it is noted that the study is carried out with the highest standard of design, and with a proven drug without unexpected side effects or disadvantages. In the literature, there seems no evidence to suspect an increased risk of blood clot formation using the drug. However, it seems clear that the incidence of complications associated with hysterectomy is quite high. It is therefore ethically fully responsible and appropriate to carry out the planned study with the desire to ensure the quality and improve hysterectomy, surgery. The project is supported by funds and receives no commercial support.

Official Title
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Peroperative Tranexamic Acid as Prophylaxis of Haemorrhage in Benign Hysterectomy - a Randomized, Placebo-controlled Trial

Conditions
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Gynecologic Surgical Procedures, Hysterectomy, Tranexamic Acid

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Women over 18 who is to undergo elective benign hysterectomy Exclusion Criteria: Known thrombophilia Active / previous thromboembolic disease Family history of thromboembolic disease (thrombophilia in the family) Hypersensitivity to any ingredient in Tranexamic acid Renal impairment Ongoing hematuria Subarachnoid hemorrhage Daily use of any type of blood thinners (Clopidogrel / Marevan / Warfarin / Nonsteroidal Antiinflammatory Drugs (not when pain is the indication)) Preoperative use of Tranexamic acid within 24 hours of the operation Known malignancy or hysterectomy as part of the investigation for suspected malignancy Insufficient understanding of the information concerning the project: language disabilities, intellectual limitations, or the like.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tranexamic Acid<br>1g Tranexamic acid iv just before surgery | Drug: Tranexamic Acid<br>* 1g Tranexamic acid iv administered over 10 minutes just before surgery<br>* Other names: Cyklokapron;|
| Placebo Comparator: Placebo<br>sterile sodium chloride 9mg/ml iv | Drug: Placebo<br>* 10 ml sodium chloride iv administered over 10 minutes just before surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative bleeding | In relation to the trial there is at set of standards to objectify blood loss during surgery. Output and input will be weighed and will form the basis of the calculated operative blood loss | 1 day (Bleeding is measured immediately after surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reduction of blood loss, Surgical complication, Hysterectomy, Antifibrinolytic Agents, Randomized Controlled Trials