Does Intravenous Tranexamic Acid Reduce Blood Loss During Vaginectomy?

Does Intravenous Tranexamic Acid Reduce Blood Loss During Vaginectomy? A Double-blind, Placebo-controlled, Randomized Trial

There are many risks for patients undergoing surgery, with blood loss and the risk of resulting anemia and blood transfusion being a common one. Decreasing blood loss with medication can be an important tool in reducing post-operative complications. Tranexamic acid (TXA) is an anti-fibrinolytic that inhibits the activation of plasminogen to plasmin. It inhibits the ability of plasminogen to dissolve fibrin networks, thus decreasing bleeding. TXA was shown in a systematic review and meta-analysis by Ker et. al in 2013 to reduce surgical blood loss by an average of 34% with an increased percentage reduction as the amount of bleeding during surgery decreased. This review also showed that a dose of 1g intravenous (IV) was sufficient in most adults with no evidence supporting a higher dose.

Vaginectomy or total colpocleisis is a surgical procedure performed for women experiencing symptomatic pelvic organ prolapse. It is performed in women who have significant vaginal vault prolapse post-hysterectomy and wish an effective treatment but accept the inability of having penetrative vaginal intercourse. It is most often performed in older patients who have multiple co-morbidities that would preclude them from having a more invasive procedure to correct their prolapse, such as an abdominal sacral colpopexy which involves the placement of surgical mesh, is a significantly longer procedure, and has more associated surgical risks.

This study will be a double-blind, placebo-controlled, randomized trial looking at whether 1g IV tranexamic acid compared with placebo reduces blood loss in women undergoing vaginectomy.

Study Overview

• Status: Recruiting
• Conditions: Pelvic Organ Prolapse
• Intervention / Treatment: Drug: Tranexamic Acid Injectable Solution; Other: Placebo

Detailed Description

There are many risks for patients undergoing surgery, with blood loss and the risk of resulting anemia and blood transfusion being a common one. Surgeons are constantly working to reduce patient morbidity by decreasing blood loss during procedures. This can be done via excellent surgical technique and meticulous hemostasis but the addition of medications can also be a valuable tool in reducing the amount of blood loss.

Tranexamic acid (TXA) is an anti-fibrinolytic that inhibits the activation of plasminogen to plasmin. It inhibits the ability of plasminogen to dissolve fibrin networks, thus decreasing bleeding. TXA was shown in a systematic review and meta-analysis by Ker et. al in 2013 to reduce surgical blood loss by an average of 34% with an increased percentage reduction as the amount of bleeding during surgery decreased. This review also showed that a dose of 1g intravenous (IV) was sufficient in most adults with no evidence supporting a higher dose.

In gynecology, oral TXA has been used for years in the management of menorrhagia and has been shown to be very effective at decreasing blood loss. In other areas of medicine the IV formulation has shown to reduce death due to bleeding in trauma patients as well as in women experiencing post-partum hemorrhage. Recent RCTs on its use in benign hysterectomy, as well as in advanced ovarian cancer surgery have shown a decrease in blood loss of more than 25% without an increase in adverse events, specifically venous thromboembolic events.

Vaginectomy or total colpocleisis is a surgical procedure performed for women experiencing symptomatic pelvic organ prolapse. It is performed in women who have significant vaginal vault prolapse post-hysterectomy and wish an effective treatment but accept the inability of having penetrative vaginal intercourse. It is most often performed in older patients who have multiple co-morbidities that would preclude them from having a more invasive procedure to correct their prolapse, such as an abdominal sacral colpopexy which involves the placement of surgical mesh, is a significantly longer procedure, and has more associated surgical risks.

Blood loss with a vaginectomy can vary but is not insignificant, especially in elderly women who may have cardiac compromise or pre-existing anemia. The average blood loss quoted in the literature for total colpocleisis varies from 135mL to 396mL, depending on the study. This gives an overall average of about 225mL. If the average patient has a blood volume of 4550mL (calculated based on 65mL/kg in women with a weight of 70kg) this represents a decrease of approximately 5%.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Colleen McDermott, MD; Phone Number: 6490 416-586-4800; Email: Colleen.McDermott@sinaihealthsystem.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Colleen D McDermott, MD; Phone Number: 6490 516-586-4800; Email: colleen.mcdermott@utoronto.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• female patients over the age of 18
• undergoing a vaginectomy by a member of the Urogynaecology department, with or without concomitant anti-incontinence mid-urethral sling

Exclusion Criteria:

• concomitant hysterectomy at the time of vaginectomy
• inability to read and speak English if no family member or interpreter available for consent process
• cognitively impaired and unable to personally sign consent
• known allergy or intolerance to TXA
• previous venous thromboembolic event
• significant renal impairment (creatinine greater than 200micromol/L or creatinine clearance less than 50mL/min)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tranexamic Acid; Tranexamic Acid Injectable Solution (1g intravenous) Single dose prior to the start of surgery, after the induction of anesthesia	Drug: Tranexamic Acid Injectable Solution; 1g IV tranexamic acid mixed in normal saline (67mL); Other Names: Cyklokapron
PLACEBO_COMPARATOR: Placebo; 67mL intravenous normal saline (0.9% sodium chloride) Single dose prior to the start of surgery, after the induction of anesthesia	Other: Placebo; 67mL IV normal saline; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin	From pre-operative to the morning after surgery	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood loss	estimated by surgical team (looking at suction and sponges)	2 hours
Change in hematocrit	From pre-operative to the morning after surgery	4 weeks

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Investigators: Principal Investigator: Colleen McDermott, MD, Mount Sinai Hospital - University of Toronto

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (ACTUAL): July 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: tranexamic acid; colpocleisis; vaginectomy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Prolapse; Pelvic Organ Prolapse; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: FPMRS McD 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes