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

Hysterectomy Clinical Trial

— PeTraH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01940419
• Other study ID #: 2011-425
• Secondary ID: 2012-005407-40
• Status: Completed
• Phase: Phase 4
• First received: September 9, 2013
• Last updated: October 21, 2015
• Start date: April 2013
• Est. completion date: October 2015

Study information

• Verified date: October 2015
• Source: Hillerod Hospital, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 332
• Est. completion date: October 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Gynecologic Surgical Procedures
• Hysterectomy
• Tranexamic Acid

Intervention

Drug:
• Tranexamic Acid
1g Tranexamic acid iv administered over 10 minutes just before surgery
• Placebo
10 ml sodium chloride iv administered over 10 minutes just before surgery

Locations

Country	Name	City	State
Denmark	Department of gynecology and obstetrics, Nordsjællands Hospital	Hillerød

Sponsors (7)

Lead Sponsor	Collaborator
Hillerod Hospital, Denmark	Central Denmark Region, Odense University Hospital, Research grant from Nordsjællands Hospital, Rigshospitalet, Denmark, The Danish hysterectomy and hysteroscopy database, The fund of Olga Bryde

Country where clinical trial is conducted

Denmark, 

References & Publications (9)

Astedt B, Liedholm P, Wingerup L. The effect of tranexamic acid on the fibrinolytic activity of vein walls. Ann Chir Gynaecol. 1978;67(6):203-5. — View Citation

Bonnar J, Sheppard BL. Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid. BMJ. 1996 Sep 7;313(7057):579-82. — View Citation

Coulter A, Kelland J, Peto V, Rees MC. Treating menorrhagia in primary care. An overview of drug trials and a survey of prescribing practice. Int J Technol Assess Health Care. 1995 Summer;11(3):456-71. — View Citation

CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14. — View Citation

Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. Review. — View 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;(3):CD001886. doi: 10.1002/14651858.CD001886.pub4. Review. — View Citation

Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;(4):CD000249. Review. — View Citation

Lukes AS, Moore KA, Muse KN, Gersten JK, Hecht BR, Edlund M, Richter HE, Eder SE, Attia GR, Patrick DL, Rubin A, Shangold GA. Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol. 2010 Oct;116(4):865-75. doi: 10.1097/AOG.0b013e3181f20177. — View Citation

Sukeik M, Alshryda S, Haddad FS, Mason JM. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J Bone Joint Surg Br. 2011 Jan;93(1):39-46. doi: 10.1302/0301-620X.93B1.24984. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No