Official Title
The HeLiX (Hemorrhage During Liver Resection: traneXamic Acid) Trial: Tranexamic Acid (TXA) Versus Placebo to Reduce Perioperative Blood Transfusion in Patients Undergoing Liver Resection: A Randomized Controlled Trial
Summary:
This is a Phase III multicentre randomized controlled trial (RCT) to evaluate the impact of
tranexamic acid (TXA) on perioperative blood transfusion in patients undergoing liver
resection. The rationale for this study includes: (1) experimental evidence supporting the
use of TXA in other surgical populations; (2) lack of evidence in patients undergoing liver
resection; (3) clinical uncertainty and extensive support amongst hepatobiliary surgeons,
anaesthesiologists, and hematologists for this proposed trial; (4) a feasible and efficient
study design; and (5) the importance of the question: incidence of blood transfusion in
patients undergoing liver resection is high, and the consequences serious. The sample size
for this study is 1230 participants.Participants enrolled in the prior Vanguard study will
proceed directly into the RCT.
Trial Description
Primary Outcome:
- Receipt of blood transfusion (% transfused): 7 days
Secondary Outcome:
- Intraoperative blood loss
- Total blood loss
- Number of packed red blood cells (PRBC) units transfused
- Postoperative incidence of symptomatic venous thromboembolic event
- Postoperative complications assessed using Clavien-Dindo Grading System
- Recurrence Free Survival (within 5 years of surgery)
- Overall Survival (within 5 years of surgery)
- Quality of Life (QOL) Assessment using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
- Quality of Life (QOL) Assessment using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Liver Module (LM)C21 Questionnaire
- Perioperative mortality
- Compare the cost of tranexamic acid (TXA) versus placebo on perioperative blood transfusion in patients undergoing liver resection
Purpose
Compelling biological rationale and indirect evidence from other settings suggest
that there is potential benefit to administering TXA to patients undergoing liver resection.
A lack of consensus in the hepatobiliary community and lack of direct evidence in patients
undergoing liver resection mandate a RCT.
Hypothesis
To determine the impact of perioperative administration of TXA to patients
undergoing liver resection on the need for blood transfusion and long-term survival.
Justification
If TXA use in liver resection resulted in an important decrease in blood
transfusions, clinical practice worldwide would be likely to change. Over 2000 patients in
Canada undergo liver resection annually and could benefit from this simple, low-cost
intervention. This intervention could easily be implemented in other countries, where many
more patients undergo liver resection annually. Furthermore, TXA may be beneficial in other
operative fields where bleeding is a major problem, including thoracic surgery, colorectal
surgery, and many others.
Objectives
The primary outcome of the RCT will be:
- Receipt of blood transfusion (% transfused): 7 days
The secondary outcomes of the RCT are:
- Intraoperative blood loss will be assessed by adding the net weight of sponges and fluid
suction (minus irrigation and intraoperative bile or other fluids in suction/sponge)
- Total blood loss (postoperative day (POD)0 - POD7) will be assessed by Gross' formula,
which uses the maximum postoperative decrease in the level of hemoglobin adjusted for
the weight and height of the patient
- Number of packed red blood cells (PRBC) units transfused (POD0 - POD7)
- Postoperative incidence of symptomatic venous thromboembolic event confirmed with either
computed tomography (CT) angiogram (for pulmonary embolism) or venous Doppler ultrasound
(for deep venous thrombosis) (within 90 days of surgery)
- Postoperative complications (within 90 days of surgery) will be determined using the
Clavien-Dindo classification
- Recurrence free survival (within 5 years of surgery) will be determined by review of
patient medical record every 6 months until 5 years post-surgery
a. Recurrence free survival is defined as the time from POD0 to the first event that is
recurrent (local or distal) cancer or death (from any cause)
-
Overall survival (within 5 years of surgery) will be determined by review of patient
medical record every 6 months until 5 years post-surgery
a. Overall survival is defined as the time from date of POD0 to death from any cause
- QOL will be determined by administering European Organization for Research and Treatment
of Cancer (EORTC) Quality of Life Questionnaire (QLQ) -C30 and the QLQ- Liver Metastases
Colorectal (LMC) 21 at baseline, 30 and 90 days following surgery
-
Perioperative mortality will be recorded between POD0 and POD7
- Economic analysis will assess impact of TXA incorporation on health care resources and
strategies for systematic utilization of TXA
Research Method
This is a Phase III multicentre randomized controlled trial (RCT) to evaluate
the impact of tranexamic acid (TXA) on perioperative blood transfusion in patients undergoing
liver resection. The trial will conceal allocation, maximize possible blinding, independently
assess the appropriateness of transfusion, use strategies to limit loss to follow-up and
crossovers, and use a conservative stopping rule. Patients will be administered a single dose
of study drug intravenously immediately after induction of anaesthesia, followed by infusion
over eight hours.
Statistical Analysis
Primary analysis will include only patients who underwent liver
resection; patients who are randomized but do not receive liver resection (usually due to
more advanced disease identified intraoperatively) will be excluded. A sensitivity analysis
will be conducted whereby all randomized patients are included in the assessment of the
primary outcome.
View this trial on ClinicalTrials.gov
