Symptoms and General Pathology

All Conditions

Hemorrhage

Coagulants

All Drugs and Chemicals

Hematinics

Tranexamic Acid

Liver Extracts

Antifibrinolytic Agents

Hemostatics

1 g TXA bolus injection + 1 g TXA infusion from induction over 8 hours

1 g saline bolus injection + 1 g saline infusion from induction over 8 hours

Tranexamic acid (TXA)

Normal saline

Paul Karanicolas, MD PhD

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.

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:

1) Receipt of blood transfusion (% transfused): 7 days

The secondary outcomes of the RCT are:

1. 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)
2. 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
3. Number of packed red blood cells (PRBC) units transfused (POD0 - POD7)
4. 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)
5. Postoperative complications (within 90 days of surgery) will be determined using the Clavien-Dindo classification
6. 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)
7. 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
8. 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
9. Perioperative mortality will be recorded between POD0 and POD7
10. 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.

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

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

Receipt of one or more RBC transfusions between Day 0 and Day 7

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

Disease recurrence is defined as the clinical presence of cancer that has either been confirmed by biopsy, has had treatment initiated, or is documented in the treating physician's notes. Five year disease recurrence from day of surgery will be evaluated approximately every 6 months until 5 years via medical record review.

Overall survival is defined as the time from date of surgery to death from any cause. It will be determined by review of patient medical record every 6 months until 5 years post-surgery.

QOL will be determined by administering the EORTC QLQ-C30 at baseline, 30 and 90 days following surgery.

QOL will be determined by administering QLQ-LMC21 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. The analysis will be using data collected in the randomized controlled trial from a societal perspective.The output of the economic analysis is the incremental cost of TXA compared to placebo (control group).

HepatoPancreaticoBiliary (HPB) Concept Team

Sunnybrook Health Sciences Centre

Neoplasms

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

This group of participants will undergo a bony tumor resection of the femur or proximal tibia and endoprosthetic reconstruction with TXA.

This group of participants will undergo a bony tumor resection of the femur of proximal tibia and endoprosthetic reconstruction.

This group of participants will undergo soft tissue sarcoma resection of the lower extremity with TXA

This group of participants will undergo soft tissue sarcoma resection of the lower extremity.

Intervention groups will receive TXA 1g TXA IVPB 10 minutes prior to incision and a second dose of 1g IVPB at the time of closure.

Tranexamic Acid (TXA)

Kyle Sweeney, MD

This study intends to determine if any correlation exists between administration of TXA or not to musculoskeletal oncology patients undergoing endoprosthetic reconstruction and blood loss and blood transfusion rates.

Resection of bony and soft tissue tumors with endoprosthetic reconstruction often presents a significant risk of perioperative blood loss requiring transfusion. Tranexamic acid (TXA) is an antifibrinolytic that is commonly used to reduce blood loss in orthopedic procedures, most often arthroplasty. The aim of this study is to determine in a randomized controlled fashion if there is any difference in perioperative blood loss and blood transfusion rates when TXA is used compared to when it is not used in patients undergoing radical resection of bone and soft tissue sarcomas with endoprosthetic reconstruction.

Participants are randomized to one of four groups. One group is the bony tumor treated with TXA, second group is the bony tumor treated without TXA, third group is the soft tissue sarcoma treated with TXA, and the fourth group is soft tissue sarcoma treated without TXA.

Tranexamic Acid in Radical Resection and Endoprosthetic Reconstruction

Tranexamic Acid in Radical Resection and Endoprosthetic Reconstruction: A Randomized Controlled Trial

Perioperative blood loss measured by the hemoglobin balance method at postoperative days 1-3.

Number of required blood transfusions up to 3 days following surgery

Surgical drain output as measured in ml for 3 days following surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The HeLiX (Hemorrhage During Liver Resection: traneXamic Acid) Trial	NCT02261415	Cancer Tumour Surgery	Tranexamic acid... Normal saline	18 Years -	Sunnybrook Health Sciences Centre
Tranexamic Acid in Radical Resection and Endoprosthetic Reconstruction	NCT04347122	Musculoskeletal... Sarcoma,Soft Ti...	Tranexamic Acid...	18 Years - 90 Years	University of Kansas Medical Center
Tranexamic Acid in Radical Resection and Endoprosthetic Reconstruction	NCT04347122	Musculoskeletal... Sarcoma,Soft Ti...	Tranexamic Acid...	18 Years - 90 Years	University of Kansas Medical Center
Tranexamic Acid in Radical Resection and Endoprosthetic Reconstruction	NCT04347122	Musculoskeletal... Sarcoma,Soft Ti...	Tranexamic Acid...	18 Years - 90 Years	University of Kansas Medical Center

Spots Global Cancer Trial Database for tranexamic acid (txa)