Tranexamic Acid Versus Placebo for Blood to Reduce Perioperative Bleeding Post-liver Resection

This study is not yet open for participant recruitment.
Verified July 2012 by Sunnybrook Health Sciences Centre
Sponsor:
Collaborator:
University of Toronto
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT01651182
First received: July 24, 2012
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to determine if tranexamic acid reduces perioperative blood loss in patients undergoing major liver resection.

Liver resection remains the optimal treatment for patients with primary or metastatic liver disease. However, extensive intraoperative blood loss remains a major risk factor for postoperative morbidity and mortality, as well as long-term survival after liver resection. Furthermore, risks of blood transfusion itself include transfusion-related acute lung injury, transfusion-associated circulatory overload, acute hemolytic transfusion reactions, bacterial contamination and severe allergic reactions.


Condition Intervention Phase
Cancer
Tumour
Surgery
Drug: Normal saline
Drug: Tranexamic Acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Tranexamic Acid Versus Placebo to Reduce Perioperative Bleeding in Patients Undergoing Major Liver Resection: A Pilot, Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:
  • Receipt of blood transfusion(s) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Transfusion of any blood product (red blood cells, fresh frozen plasma, platelets, or albumin) will be guided by a standardized protocol. Red blood cells will be transfused for Hgb<70, or Hgb 70-90 based on medical judgment with an indication provided by the transfusing clinician (coronary ischemia, hemodynamic instability, ongoing blood loss, etc). Fresh frozen plasma will be transfused for INR > 1.5 with active bleeding. Platelets will be transfused only if the patient is bleeding with platelet count < 50 x 109/L and cryoprecipitate only if patient is bleeding with fibrinogen < 1.0 g/L.


Secondary Outcome Measures:
  • Total blood loss as assessed by Gross' formula [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Intraoperative blood loss assessed by adding net weight of sponges and fluid suction (minus irrigation) [ Time Frame: Duration of anaesthesia ] [ Designated as safety issue: No ]
  • Total volume of blood transfused [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Post-operative incidence of symptomatic venous thromboembolic event [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Other post-operative complications [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: September 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Normal saline Drug: Normal saline
Active Comparator: Tranexamic Acid Drug: Tranexamic Acid
Patients will be administered a single dose of 1g tranexamic acid intravenously, immediately after induction of anaesthesia followed by 1g infusion over 8 hours.
Other Names:
  • Cyclokapron
  • Antifibrinolytic
Drug: Tranexamic Acid

Detailed Description:

Liver resection remains the optimal treatment for patients with primary or metastatic liver malignancies, benign liver tumors, and some biliary diseases. Despite improvements such as advances in preoperative imaging and evaluation of liver functional reserve, extensive intraoperative blood loss remains a major risk factor for postoperative morbidity and mortality, as well as long-term survival after liver resection.

Several strategies to reduce blood loss during liver resection have been developed and tested including operative and non-operative interventions. Operatively, surgeons may use sophisticated methods of liver dissection and parenchymal transection including ultrasonic dissectors, hydrodissectors, bipolar cautery, stapling devices, and more. Surgeons may also selectively reduce the blood flow to the liver during liver resection by continuously or intermittently clamping the portal vein and hepatic artery (the Pringle Maneuver). The anaesthesiologist has a crucial role in reducing blood loss and transfusion requirements by maintaining a low central venous pressure (CVP) during parenchymal transection. These advances have resulted in substantially less blood loss during liver surgery compared with prior decades, however bleeding remains a problem during major liver resection with up to 30-40% of patients in recent series receiving blood products.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient undergoing anticipated major liver resection (> 2 hepatic segments), as assessed by the operating surgeon
  • Age >18

Exclusion Criteria:

  • Previously enrolled in this study
  • Platelet count less than 100,000/mm3
  • Known hereditary coagulopathy (INR>1.5)
  • Severe anemia (hemoglobin levels less than 90 g/l)
  • Documented arterial or venous thrombosis at screening or in past three months
  • Anticoagulants (other than LMWH or heparin in prophylactic doses to prevent deep vein thrombosis), direct thrombin inhibitors or thrombolytic therapy administered or completed within last week
  • Cirrhosis
  • Hepatectomy associated with planned vascular or biliary reconstruction
  • Disseminated intravascular coagulation
  • Severe renal insufficiency (CrCl<30)
  • History of seizure disorder
  • Pregnant or lactating
  • Hypersensitivity to tranexamic acid or any of the ingredients
  • Unable to receive blood products (i.e. difficulty with cross matching, refuses blood transfusion, or a past history of unexplained severe transfusion reaction)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01651182

Contacts
Contact: Jenny Lam-MCulloch 416-480-6100 ext 85391 jenny.lam-mcculloch@sunnybrook.ca

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre Not yet recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Paul Karanicolas, MD PhD    416-480-4832    paul.karanicolas@sunnybrook.ca   
Contact: Jenny Lam-McCulloch, MSc    416-480-6100 ext 85391    jenny.lam-McCulloch@sunnybrook.ca   
Principal Investigator: Paul Karanicolas, MD PhD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
University of Toronto
Investigators
Principal Investigator: Paul Karanicolas, MD PhD Sunnybrook Health Sciences Centre
  More Information

No publications provided

Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT01651182     History of Changes
Other Study ID Numbers: SHSC_PK_TA-Liver
Study First Received: July 24, 2012
Last Updated: July 25, 2012
Health Authority: Canada: Health Canada

Keywords provided by Sunnybrook Health Sciences Centre:
Blood transfusion
Blood loss
Postoperative complications
Outcome

Additional relevant MeSH terms:
Hemorrhage
Pathologic Processes
Antifibrinolytic Agents
Tranexamic Acid
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014