Clinical trial NCT01940419: Testing of the Drug Tranexamic Acids as Prophylaxis of Bleeding in Benign Surgical Removal of the Uterus
Official title: Peroperative Tranexamic Acid as Prophylaxis of Haemorrhage in Benign Hysterectomy - a Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gynecologic Surgical Procedures
Hysterectomy
Tranexamic Acid
Keywords: Reduction of blood loss
Surgical complication
Hysterectomy
Antifibrinolytic Agents
Randomized Controlled Trials
Lead sponsor: Hillerod Hospital, Denmark
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Odense University Hospital
name: Central Denmark Region
name: Research grant from Nordsjællands Hospital
name: The fund of Olga Bryde
name: The Danish hysterectomy and hysteroscopy database
First posted: 2013-09-12
Enrollment: 332
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Intraoperative bleeding
timeFrame: 1 day (Bleeding is measured immediately after surgery)
Secondary outcomes:
Other outcomes:
Locations:
city: Hillerød
country: Denmark
facility: Department of gynecology and obstetrics, Nordsjællands Hospital
Study officials:
affiliation: Department of gynecology and obstetrics, Nordsjællands Hospital, 3400 Hillerød
name: Märta F Topsøe, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, Ker K. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011 Mar 16;2011(3):CD001886. doi: 10.1002/14651858.CD001886.pub4.
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