The Effect on Blood Loss of Topical and Intravenous Tranexamic Acid in Cardiac Surgery Patients

The Effect on Blood Loss of Topical and Intravenous Tranexamic Acid in Cardiac Surgery Patients: a Randomized Placebo-controlled Trial

It remains still unclear whether topical tranexamic acid has an added value besides the administration of intravenously tranexamic acid. We hypothesize that the addition of topical tranexamic acid, besides intravenous administration of tranexamic acid, results in a 25% reduction of post-operative blood loss after cardiac surgery.

The aim of this study is to determine whether the application of topical tranexamic acid reduces the 12 hours postoperative blood loss by 25% in patient scheduled for cardiac surgery on cardiopulmonary bypass, whereby intravenous tranexamic acid is administrated.

Just before sternal closure, 250 subjects receives pericardial lavage with 2 gr tranexamic acid in 200 ml normothermic saline solution (NaCl 0.9%), 250 subjects receives pericardial lavage with 200 ml normothermic saline solution without TA and 250 subjects (control group) receives no pericardial lavage. The main study parameter is 12 hours post-operative blood loss and is assessed by 12 hours post-operative chest tube production.

Study Overview

• Status: Completed
• Conditions: Blood Loss; Cardiac Surgery; Tranexamic Acid
• Intervention / Treatment: Drug: Saline; Drug: 2 gr tranexamic acid

• Study Type: Interventional
• Enrollment (Actual): 750
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Breda, Netherlands, 4800 RK
    • Amphia Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gender; male/ female
• Age: ≥ 18 year

• Elective cardiac surgical patients

  • Coronary artery bypass graft (CABG) (conventional, E.CCO)
  • Aortic valve replacement (AVR) (conventional)
  • Mitral valve replacement (MVR)/ Mitral valve repairment (MPL) (conventional)
  • Tricuspid valve replacement (TVR) / Tricuspid valve repairment (TPL)
  • Bentall
  • Combined procedure (e.g. CABG/ AVR, MVR/AVR, AVR/Maze)

Exclusion Criteria:

• MVR/MPL (minimal invasive, Port Access Surgery)
• Maze (minimal invasive, via Thoracoscopy)
• AVR (minimal invasive, via mini Sternotomy)
• off-pump procedures
• Emergency operations
• Patient with increased or decreased blooding tendency (FV leiden, prot C, S deficiency, anti-thrombin deficiency, prothrombin mutation)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: pericardial lavage with 200 ml normothermic saline solution; According to the anaesthetic protocol of the Amphia Hospital (Breda, the Netherlands), all patients scheduled for cardiac surgery receive intravenously 2 gr TA before sternal incision and 2 gr TA after cardiopulmonary bypass. This arm also receives pericardial lavage with 200 ml normothermic saline solution without tranexamic acid.	Drug: Saline; This group receives pericardial lavage with 200 ml normothermic saline solution without tranexamic acid
No Intervention: No pericardial lavage; According to the anaesthetic protocol of the Amphia Hospital (Breda, the Netherlands), all patients scheduled for cardiac surgery receive intravenously 2 gr TA before sternal incision and 2 gr TA after cardiopulmonary bypass. In this arm the subjects receives as in standard care no pericardial lavage.
Experimental: 2 gr tranexamic acid diluted in 200 ml normothermic saline; According to the anaesthetic protocol of the Amphia Hospital (Breda, the Netherlands), all patients scheduled for cardiac surgery receive intravenously 2 gr TA before sternal incision and 2 gr TA after cardiopulmonary bypass. This arm receives also pericardial lavage with 2 gr TA diluted in 200 ml normothermic saline solution (NaCl 0.9%).	Drug: 2 gr tranexamic acid; This group receives pericardial lavage with 2 gr tranexamic diluted in 200 ml normothermic saline solution (NaCl 0.9%).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Blood Loss	The primary study parameter is 12 hours postoperative blood loss and is assessed by postoperative chest tube production. Postoperative chest tube production 12 hours after surgical procedure	12 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Requiring Surgical Re-exploration	the secondary objective of this study is to determine whether pericardial lavage with saline gives an improvement in haemostasis, compared with no pericardial lavage, resulting in a reduction of surgical re-explorations and post-operative 12-hour blood loss. The choice for a surgical re-exploration will be decided according to the ICU protocol.	participants will be followed for the duration of ICU stay, an expected average of 2 days
Total Red Blood Cell Transfusions (Cumulative of Pre, Peri and Postoperative Period)	The amount of red blood cell transfusions the patient receive pre, peri and postoperatively during their stay in the hospital.	participants will be followed for the duration of ICU stay, an expected average of 2 days/ And participants will be followed for the duration of hospital stay, an expected average of 3 weeks

Collaborators and Investigators

• Sponsor: Amphia Hospital
• Investigators: Principal Investigator: Thierry Scohy, Amphia Hospital

Publications and helpful links

General Publications

• Mahaffey R, Wang L, Hamilton A, Phelan R, Arellano R. A retrospective analysis of blood loss with combined topical and intravenous tranexamic acid after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2013 Feb;27(1):18-22. doi: 10.1053/j.jvca.2012.08.004. Epub 2012 Oct 10.
• De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, Schiavello R, Possati GF. Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. J Thorac Cardiovasc Surg. 2000 Mar;119(3):575-80. doi: 10.1016/s0022-5223(00)70139-5.
• Baric D, Biocina B, Unic D, Sutlic Z, Rudez I, Vrca VB, Brkic K, Ivkovic M. Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg. 2007 Mar;31(3):366-71; discussion 371. doi: 10.1016/j.ejcts.2006.12.003. Epub 2007 Jan 10.
• Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol. 2006 May;23(5):380-4. doi: 10.1017/S0265021505001894. Epub 2006 Jan 27.
• Spegar J, Vanek T, Snircova J, Fajt R, Straka Z, Pazderkova P, Maly M. Local and systemic application of tranexamic acid in heart valve surgery: a prospective, randomized, double blind LOST study. J Thromb Thrombolysis. 2011 Oct;32(3):303-10. doi: 10.1007/s11239-011-0608-3.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: July 5, 2013
• First Posted (Estimate): July 10, 2013

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 1, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: cardiac surgery; blood loss; tranexamix acid
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: TA-1251; 2013-000774-30 (EudraCT Number)