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 multicentre Vanguard 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. Different regions
of Canada are well represented in the selection of study sites and five major sites have
committed to participate in the Vanguard trial, including: Sunnybrook Health Sciences Centre
(Toronto), University Health Network (Toronto), Foothills Medical Centre (Calgary), McGill
University Health Centre (Montreal), and Queen Elizabeth II Health Sciences Centre (Halifax).
We will enroll 400 patients in this Vanguard study. This Vanguard study will assist us in
determining the feasibility and planning of a definitive multicentre RCT across Canada. If
the Vanguard study confirms feasibility, we will expand the trial to additional sites and
proceed directly into the definitive trial (planned sample size = 1230 patients). The
following is a brief schema and study outline of the trial.
Trial Description
Primary Outcome:
Secondary Outcome:
- Eligible patients who consent to participate
- Ability to randomize patients and administer intervention
- Ability to collect complete perioperative data to 90 days
- Adherence with perioperative blood transfusion guidelines
- Assessment of transfusion incidence
Purpose Results of this study will provide essential feasibility data for planning and
conducting a large national trial that will definitively establish the impact of TXA on blood
transfusion in patients undergoing liver resection. There are special challenges related to
patient recruitment, adherence to detailed transfusion protocols, and data collection, all of
which the TXA Vanguard trial will help to address. Success of the TXA Vanguard trial will be
based on the ability to achieve each of the seven feasibility objectives: (1) Proportion of
patients screened who meet the eligibility criteria for the definitive trial; (2) Proportion
of eligible patients who consent to participate in this trial; (3) Adherence to randomized
intervention; (4) Missing data including operative details, blood loss, blood transfusions,
and complications; (5) Assess adherence with perioperative blood transfusion guidelines; (6)
Assess transfusion incidence; (7) Estimate the resource requirements for each participating
site to conduct the full RCT.
Hypothesis Results of this study will provide essential feasibility data for planning and
conducting a large national trial that will definitively establish the impact of TXA on blood
transfusion in patients undergoing liver resection.
Justification Were the investigators to demonstrate that 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. There are practical challenges related
to patient recruitment, adherence to detailed transfusion protocols and data collection, all
of which the TXA pilot Vanguard will address.
Objectives
Before embarking on a national definitive RCT to address the objectives listed in the Purpose
above, this Vanguard trial has seven specific feasibility objectives:
1. To determine the proportion of patients screened at five major hepatopancreaticobiliary
centres that meet the eligibility criteria for a definitive trial.
2. To calculate the proportion of eligible patients who consent to participate in this
trial.
3. To assess the ability to randomize patients and adherence with the group allocation.
4. To examine the ability to collect complete perioperative data on participants, including
operative details, blood loss, blood transfusions, and complications.
5. To assess adherence with perioperative blood transfusion guidelines.
6. Assess transfusion incidence.
7. To estimate the resource requirements for each participating site to conduct the full
RCT.
The Primary Outcome is the length of time required to enroll 200 patients into this Vanguard
trial.
Research Method This is a multicentre Vanguard 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 The results of this Vanguard trial will be used to assess the
feasibility and inform design issues of the full RCT. We will present point estimates of
feasibility events, including adherence to protocol and accrual, as proportions with 95% CI.
We will present continuous data as means and standard deviations, or medians and
inter-quartile ranges, as appropriate.
View this trial on ClinicalTrials.gov
