The HeLiX (Hemorrhage During Liver Resection: traneXamic Acid) Trial

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: 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 200 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:

• Mean centre recruitment

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. 6. 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