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

Pancreatic Cancer Clinical Trial

— TMGS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01655641
• Other study ID #: # WS2017115
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: July 23, 2012
• Last updated: October 14, 2012
• Start date: July 2012
• Est. completion date: July 2014

Study information

• Verified date: October 2012
• Source: Tribhuvan University Teaching Hospital, Institute Of Medicine.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Nepal: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 118
• Est. completion date: July 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colon Cancer
• Gastric Cancer
• Hepatocellular Cancer
• Liver Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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:
• Standard of care
Includes routine surgical care involved in preventing blood loss during and after surgery.

Locations

Country	Name	City	State
Nepal	Tribhuvan University Teaching Hospital	Kathmandu	Kathmandy

Sponsors (2)

Lead Sponsor	Collaborator
Tribhuvan University Teaching Hospital, Institute Of Medicine.	Pfizer

Country where clinical trial is conducted

Nepal, 

References & Publications (14)

American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task — View Citation

Blajchman MA, Vamvakas EC. The continuing risk of transfusion-transmitted infections. N Engl J Med. 2006 Sep 28;355(13):1303-5. — View Citation

Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year exper — View Citation

Clavien PA, Sanabria JR, Strasberg SM. Proposed classification of complications of surgery with examples of utility in cholecystectomy. Surgery. 1992 May;111(5):518-26. — View Citation

Colomina MJ, Bagó J, Fuentes I. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine 2008; 33: 2577-80. Spine (Phila Pa 1976). 2009 Jul 15;34(16):1740- — View Citation

CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaom — View Citation

Crescenti A, Borghi G, Bignami E, Bertarelli G, Landoni G, Casiraghi GM, Briganti A, Montorsi F, Rigatti P, Zangrillo A. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. — View Citation

Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. Review. — View Citation

Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine (Phila Pa 1976). 2008 No — View Citation

Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, McClelland B, Laupacis A, Fergusson D. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001886. Review. Update in: Cochra — View Citation

Katsaros D, Petricevic M, Snow NJ, Woodhall DD, Van Bergen R. Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients. Ann Thorac Surg. 1996 Apr;61(4):1131-5. — View Citation

Mannucci PM, Levi M. Prevention and treatment of major blood loss. N Engl J Med. 2007 May 31;356(22):2301-11. Review. — View Citation

Urban MK, Beckman J, Gordon M, Urquhart B, Boachie-Adjei O. The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery. Spine (Phila Pa 1976). 2001 May 15;26(10):1152-6. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary objective of the study is to compare transfusion requirements and Mortality in patients receiving Tranexamic acid (Cyklokapron®) and those not receiving it.		30 days	Yes
Secondary	Secondary outcome measure	Re-bleeding events	30days	Yes
Secondary	Secondary Outcome measure	Need for surgical intervention	30 days	Yes
Secondary	Secondary outcome measure	Length of stay in ICU	30 days	Yes