Study of Tranexamic Acid for Reducing Blood Requirement in Patients Undergoing Major Gastro-intestinal Surgery (TMGS)

October 14, 2012 updated by: Dr Bikal Ghimire, Tribhuvan University Teaching Hospital, Institute Of Medicine.

Role of Tranexamic Acid for Reducing Blood Loss in Patients Undergoing Major Gastro-intestinal Surgery

Primary objective of the study is to compare requirement of blood transfusion and mortality in patients receiving Tranexamic acid (Cyklokapron®) and those not receiving it.

Secondary objective is to; assess the re-bleeding events; need for surgical intervention; length of stay in Intensive care unit in between the two groups.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background:

Surgery is one of the major causes of blood loss. Though major blood loss is associated with cardiovascular procedures, liver transplantation etc, transfusions are frequently required in major gastrointestinal surgeries such as Whipples Procedure; Liver resections etc.1 Transfusion is associated with numerous risks such as mismatched transfusion, allergic reactions, transmission of infections, and acute lung injury etc.2 Though transfusion can be life saving, it is essential to rationalize transfusion whenever possible.

A number of agents have been tried in the past that stabilizes the coagulation system in the body minimizing blood loss; an ideal agent is yet to be found. Tranexamic acid, {trans-4-(aminomethyl) cyclohexanecarboxylic acid} is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin.3 Tranexamic acid was first approved by the FDA in 1986 as an injection, under the brand name Cyklokapron®. This agent has been in use for last 40 years in many traumatic conditions with various successes with waxing and waning of its use. There has been a resurgence of interest in its use lately as more is known of this molecule. Tranexamic acid has been found to be very effective in orthopedic surgeries.4,5,6 A Cochrane review on 'antifibrinolytic use for minimizing perioperative blood transfusion' involving 21 trails of tranexamic acid vs. control in patients undergoing orthopedic surgery showed significant reduction in blood transfusion and perioperative blood loss.7 Randomized trial of tranexamic acid done on cardiac surgery patients as early as 1996 had shown significant reduction of red-cell transfusion and other blood products.8 CRASH 2 Trial (Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage) is a large placebo-controlled trial studying the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events and blood transfusion in adult trauma patients with significant hemorrhage. It involved 274 hospitals across 40 countries and started in 2005 and concluded that tranexamic acid could safely reduce the risk of death in bleeding trauma patients.9 Intraoperative use of low dose tranexamic acid has been observed to be safe and effective in reducing the rate of perioperative blood transfusions in patients undergoing radical retropubic prostatectomy.10 It has also been approved by FDA for use in menorrhagia.

Though it is being used in gastrointestinal bleeding and abdominal trauma, it is not routinely used in major gastrointestinal surgeries. In this context, this study is undertaken to evaluate the efficacy of tranexamic acid in major gastrointestinal surgeries.

Investigators hypothesize that addition of Tranexamic acid, an antifibrinolytic agent, to conventional therapy will lead to an improved outcome characterized by lower transfusion requirements.

Detailed Description:

After informed consent is obtained patients will be randomized to receive either Tranexamic acid along with the conventional therapy or conventional therapy only. All patients undergoing major gastrointestinal surgery (involving resection of stomach, pancreas, esophagus, colon, liver) will be included for the surgery and this will be decided by the surgeon prior to the surgery. Randomization will be done prior to surgery by the closed envelope method. Tranexamic acid will be administered in a loading dose of 1 gm intravenously over 10 minutes, 30minutes before surgery followed by 10mg / kg body weight, 8 hourly for 5 days. Post operative blood requirements and the fluids in the drain will be monitored along with the HB/PCV level every day for 7 days or until the drains are removed.

Tranexamic acid is an antifibrinolytic agent that has been shown to be associated with reduced bleeding and transfusion requirement in surgical patients. We would like to randomize patients to receive either Tranexamic acid in addition to conventional therapy or the conventional therapy only and monitor outcome. Intraoperative blood requirements are usually governed by the intraoperative blood loss hence, only post operative blood transfusions will be taken as the 'Post operative blood requirements' for these patients. Post operative complications will be assessed according to the Clavien-Dindo Classification system for surgical complications.11,12,13 Patients will be monitored until discharge and after 30 days to assess for any complication. Duration of ICU stay, duration of admission and Mortality will be monitored for both groups of patients.

Requirement for Transfusion will be assessed by the operating surgeon. Patients will be monitored post operatively with the hemoglobin and PCV level and the drain fluid amount and nature. Transfusion will be given for ongoing blood loss at the discretion of the operating surgeon or when hemoglobin level is <8milligram per deciliter hemoglobin or hematocrit value of less than 24 percent in healthy individual or < 10mg/dl in high risk patients.14 Transfusion of Fresh Frozen Plasma (FFP) and Platelet Rich Plasma (PRP) will be done as required.

This study should provide us with information about the efficacy of this medicine in patients undergoing major GI surgery. Data from this trial will provide us information about utility of pursuing this modality of therapy.

Study Type

Interventional

Enrollment (Anticipated)

118

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nepal
    • Kathmandy
      • Kathmandu, Kathmandy, Nepal, 0977
        • Tribhuvan University Teaching Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

All patients undergoing major GI surgery that includes resection of:

  • Esophagus
  • Stomach
  • Spleen
  • Liver
  • Pancreas
  • Colon

Exclusion Criteria:

  • Pre op HB less than 10mg/dl
  • Pregnant or lactating women
  • On anticoagulation therapy
  • Patients with history of thromboembolism
  • Patients with history of myocardial infarction or ischemic cerebrovascular accident
  • Patient with end stage renal disease
  • Patients with DNR status
  • Patients with known bleeding abnormalities
  • Emergency/unplanned surgeries
  • Patients with known allergy/contraindications to Tranexamic acid
  • Patients not capable of giving consent for medical reasons (psychiatric etc)\
  • Patients not giving consent or opting to withdraw from the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Tranexamic acid arm

Along with the standard of care (routine surgical care involved in preventing blood loss during surgery) this arm will receive drug Tranexamic acid

1gm stat, preoperatively (30 mins) 10mg / kg body weight, 8 hourly for 5 days via IV for non-renal impaired subjects.

Alternate IV dosing for renally-impaired subjects: 10mg/Kg BID (1.36 - 2.83 mg/dl clearance); 10mg/Kg QD (2.84 - 5.66 mg/dl clearance; and 10mg/Kg Q48H or 5mg/Kg (.5.66mg/dl clearance)
Drug: Tranexamic acid

Drug: Tranexamic acid

1gm stat, preoperatively (30 mins) 10mg / kg body weight, 8 hourly for 5 days via IV For non-renal impaired subjects.

Alternate IV dosing for renally-impaired subjects: 10mg/Kg BID (1.36 - 2.83 mg/dl clearance); 10mg/Kg QD (2.84 - 5.66 mg/dl clearance; and 10mg/Kg Q48H or 5mg/Kg (.5.66mg/dl clearance)

Other Names:
  • Cyklokapron®
ACTIVE_COMPARATOR: Standard of care arm
Includes routine surgical care involved in preventing blood loss during and after surgery.
Other: Standard of care
Includes routine surgical care involved in preventing blood loss during and after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Primary objective of the study is to compare transfusion requirements and Mortality in patients receiving Tranexamic acid (Cyklokapron®) and those not receiving it.
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary outcome measure
Time Frame: 30days
Re-bleeding events
30days
Secondary Outcome measure
Time Frame: 30 days
Need for surgical intervention
30 days
Secondary outcome measure
Time Frame: 30 days
Length of stay in ICU
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tribhuvan University Teaching Hospital, Institute Of Medicine.

Collaborators

Pfizer

Investigators

  • Principal Investigator: Bikal Ghimire, MS, Tribhuvan University, Nepal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (ANTICIPATED)

June 1, 2013

Study Completion (ANTICIPATED)

July 1, 2014

Study Registration Dates

First Submitted

July 23, 2012

First Submitted That Met QC Criteria

July 30, 2012

First Posted (ESTIMATE)

August 2, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

October 16, 2012

Last Update Submitted That Met QC Criteria

October 14, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • # WS2017115

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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