The objective of this study is to determine the effect of 1g of IV tranexamic acid given within 1 hour pre-operatively on intraoperative blood loss at time of hysterectomy.

Brief Title

IV Tranexamic Acid Prior to Hysterectomy

Official Title

IV Tranexamic Acid Prior to Hysterectomy for Reduction of Intraoperative Blood Loss: A Randomized Placebo-Controlled Trial

Brief Summary

The objective of this study is to determine the effect of 1g of IV tranexamic acid given <br /> within 1 hour pre-operatively on intraoperative blood loss at time of hysterectomy.

Detailed Description

Tranexamic acid (TXA) is a synthetic lysine analog that inhibits plasmin fibrinolysis. It may
be administered orally, intravenously, or topically, with a rapid onset of action (tmax =
appx 3 hours) and 11-hour half-life. It is 6 to 10 times more potent than aminocaproic acid,
another commonly used synthetic antifibrinolytic agent. Typical IV dosing is 10 mg/kg
followed by infusion of 1mg/kg/hour, or simply 1g intravenously in one dose.

The efficacy of tranexamic acid in control of hemorrhage in trauma patients has been reported
extensively. The CRASH-2 trial collaborators randomized 20,211 adult trauma patients with
significant bleeding or at risk of significant bleeding within 8 hours of injury to IV
tranexamic acid or placebo. All-cause mortality was significantly reduced with tranexamic
acid (RR .91; p = .0035). Additionally, risk of death due to bleeding was significantly lower
in those receiving tranexamic acid (RR .85; p = .0077). No differences in risk of vascular
occlusive events were noted. Further analysis revealed reduced risk of death from bleeding if
TXA was given within 3 hours of injury; treatment administered after 3 hours from injury
increased the risk of death due to bleeding.

Administration of TXA during elective surgery has also been investigated. A 2011 systematic
review of 252 randomized trials of patients undergoing elective surgery across disciplines
included administration of TXA, aminocaproic acid, and aprotinin. TXA administration reduced
the risk of transfusion peri-operatively (RR .61). A 2012 meta-analysis of TXA use in both
elective an emergency surgery revealed that TXA reduced the risk of transfusion by one-third.
The effect of TXA on risk of myocardial infarction, deep vein thrombosis, and pulmonary
embolism was not statistically significant.

The utility of TXA appears to extend to obstetric hemorrhage. Several published studies exist
analyzing its use in prevention of postpartum hemorrhage, though the drug is not considered
standard for prevention or treatment of this condition. A pilot randomized open-label trial
of IV TXA in women with postpartum hemorrhage over 800cc reported a lower median blood loss
between groups, though the effect was modest. Additionally, significantly fewer women in the
TXA group required transfusion or invasive procedures. A recent Cochrane review reports on
twelve trials of low risk women undergoing cesarean section or spontaneous birth who received
uterotonics with or without the addition of TXA. TXA was effective in decreasing estimated
blood loss over 1 liter in women undergoing cesarean section. Mean blood loss was
significantly lower in women receiving TXA (mean difference -77.79mL); effect was similar for
women undergoing cesarean section and vaginal birth. Finally, the WOMAN trial is a large,
ongoing, placebo-controlled trial examining the effect of early TXA administration in
clinically diagnosed postpartum hemorrhage.

The use of TXA in the management of acute and abnormal uterine bleeding has been reported,
and is FDA-approved for treatment of menorrhagia. One randomized study of oral TXA in the
treatment of ovulatory menorrhagia reported a 45% decrease in mean menstrual blood loss with
use of TXA as compared with placebo. Other studies have echoed these findings, with TXA more
effective than NSAIDs but less effective than the levonorgestrel intrauterine device (IUD) in
decreasing menstrual blood loss. More recently, a double-blind, placebo-controlled
randomized-controlled trial (RCT) confirmed a significant decrease in menstrual blood
loss(mean -69cc), improvements in social/physical limitations caused by menorrhagia and
self-perceived menstrual blood loss. No data exist examining the efficacy of IV TXA in the
management of acute or severe uterine bleeding.

Few studies have specifically examined the utility of prophylactic TXA in reducing mean blood
loss during hysterectomy or other gynecologic procedures. In one study of patients undergoing
endometrial ablation and endoscopic endometrial resection, intraoperative and postoperative
IV TXA significantly decreased total blood loss. In patients undergoing major debulking
surgery for gynecologic cancers, administration of IV TXA has been shown to decrease
intra-operative blood loss by 30%. One well-designed study of women with advanced-stage
ovarian cancer randomized patients to 15 mg/kg IV TXA or the same volume of placebo
immediately before surgery. Outcomes included significantly lower mean estimated blood loss
and decreased need for transfusion in the TXA group.

This study sought to determine whether a single preoperative dose of IV tranexamic acid
effectively reduces intraoperative blood loss and need for transfusion in patients undergoing
laparoscopic, abdominal, or vaginal hysterectomy for benign indications.

Objective:

To determine the effect of 1g of IV tranexamic acid given within 1 hour pre-operatively on
intraoperative blood loss at time of hysterectomy.

Primary endpoint:

Estimated blood loss as determined by anesthesia and surgeon at time of hysterectomy,
difference between post-operative and pre-operative hemoglobin, length of hospital stay,
length of procedure, need for blood transfusion and post-operative venous thromboembolic
events.

Treatment Dosage and Administration:

1g IV tranexamic acid or 100ml 0.9% sodium chloride solution administered within 1 hour of
the start of the procedure