Topical Application of Tranexamic Acid to Reduce Post-operative Bleeding in Coronary Artery Bypass Surgery

Coronary Artery Disease Clinical Trial

Official title:

Topical Application of Tranexamic Acid to Reduce Post-operative Bleeding in Coronary Artery Bypass Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01519245
• Other study ID #: 67452-01
• Status: Completed
• Phase: Phase 3
• First received: January 17, 2012
• Last updated: May 27, 2013
• Start date: December 2011
• Est. completion date: June 2012

Study information

• Verified date: May 2013
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The goal of this project is to determine whether the use of tranexamic acid, a clot-promoting drug, applied topically over the heart in coronary artery bypass graft surgery (CABG) will reduce post operative blood loss. The investigators' hypothesis is that the use of a tranexamic acid-containing cardiac bath prior to chest closure will result in a statistically significant reduction in blood loss and transfusion requirements in patients who undergo CABG.

Description:

Bleeding is expected during major surgeries. In patients who undergo CABG, the risk for bleeding is increased because of the need for intra-operative anticoagulation, or thinning, of patient blood. This anticoagulation is necessary to reduce the risk of thrombosis potentially precipitated by the cardiopulmonary bypass machine, which pumps blood throughout the body while the surgeon operates on the heart.

Strategies are currently used in the operating room to minimize blood loss and the need for allogenic blood transfusion during and after cardiac surgeries. These strategies include the use of intravenous antifibrinolytic agents, intra-operative red blood cell salvage devices, and topical fibrin sealants. Although the risk of infection from a blood transfusion is very small with modern methods of blood screening, the risk of developing a transfusion reaction is possible and not predictable. Therefore, it is preferred to avoid administering a blood transfusion unless absolutely necessary.

The use of topical antifibrinolytic agents has been explored to further reduce blood loss in cardiac surgery. Several trials have been published in the literature since 1993 evaluating the efficacy of various antifibrinolytic medications applied topically, as a cardiac bath, prior to chest closure in CABG patients to reduce post-operative blood loss and potential need for blood transfusion.

The applicability of the methodology utilized in these studies, however, is limited in the context of the current Canadian practices of cardiac surgery. Considerable differences in the perioperative strategies of these trials are seen, in comparison to current North American practices of cardiac surgery. These trials also compared use of topically applied antifibrinolytic agents, including the lysine analogue tranexamic acid, to a control in the absence of intravenous antifibrinolytic agents. The use of intravenous lysine analogues to reduce peri-operative bleeding has now become a near-standard of care in CABG patients.

Currently, the only available antifibrinolytic agent in Canada is the lysine analogue tranexamic acid. This drug is widely used administered as an intravenous preparation in cardiac surgery because its safety profile and reduction in blood loss and frequency of blood transfusion.

There is presently no published randomized controlled trial evaluating blood loss in CABG patients who have received intravenous tranexamic acid, plus topical tranexamic acid or placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: June 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criterion:

• Patients scheduled for elective or urgent CABG of two to six vessels

Exclusion Criteria:

Preoperative:

• Hemoglobin of less than 110g/L

• Under 18 years of age

• Body mass less than 75kg

• Presence of an intra-aortic balloon pump

• Emergency surgery, requiring operative intervention within 24 hours of consultation to the cardiac surgery team

• Need for cardiac surgical intervention in addition to planned CABG (with the exception of patent foramen ovale closure)

• Ejection fraction (EF) of less than 50%, as determined by echocardiogram or angiography

• Pulmonary hypertension with pulmonary artery pressures greater than 60mmHg (as estimated by right ventricular systolic pressure (RVSP))

• Presence of infectious endocarditis

• Hepatic failure with impaired liver function, including International Normalized Ratio (INR) greater than 1.5

• Known diagnosed bleeding disorder

• History of heparin induced thrombocytopenia and thrombosis (HITT)

• Renal failure with pre-operative creatinine greater than 200ml/min or oliguria with urine output less than 10ml/hour

• Allergy to tranexamic acid

• Pregnancy

Intraoperative:

• Discovery of infectious endocarditis

• Need for cardiac surgical intervention in addition to planned coronary CABG

• Development of allergic reaction to tranexamic acid following intravenous infusion

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia
• Postoperative Hemorrhage

Intervention

Drug:
• Tranexamic Acid
Solution containing 2 grams (20mL) tranexamic acid + normal saline (50mL), for a total volume of 70mL poured over the heart as a 'cardiac bath' prior to sternotomy closure near the end of surgery. Total duration of immersion is approximately 10 minutes, until mediastinal chest tubes are connected to suction.
• normal saline
A total volume of 70mL of normal saline poured over the heart as a 'cardiac bath' prior to sternotomy closure near the end of surgery. Total duration of immersion is approximately 10 minutes, until mediastinal chest tubes are connected to suction. Identical in appearance to the trial drug, and is visually indistinguishable.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Saskatchewan	Saskatoon Health Region

References & Publications (5)

Abrishami A, Chung F, Wong J. Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis. Can J Anaesth. 2009 Mar;56(3):202-12. doi: 10.1007/s12630-008-9038-x. Epub 2009 Feb 12. Review. — View Citation

Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol. 2006 May;23(5):380-4. Epub 2006 Jan 27. — View Citation

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. Epub 2007 Jan 10. — View Citation

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. — View Citation

Fawzy H, Elmistekawy E, Bonneau D, Latter D, Errett L. Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial. J Cardiothorac Surg. 2009 Jun 18;4:25. doi: 10.1186/1749-8090-4-25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Volume of Blood Loss From Mediastinal Chest Tubes at Time of Removal (Assuming the Total Volume of Loss is Blood).	According to standard practice, research participants were be transferred to the intensive care unit (ICU) for post-operative monitoring. Measurement of chest tube output began immediately on arrival to the ICU. Hourly measurements were recorded. Data collection ended upon chest tube removal, or return to the operating room for exploratory surgery due to massive blood loss. As per ICU protocol, chest tubes were be removed when blood loss was recorded to be less than 200mL after six consecutive hours.	From ICU admission post-operatively to mediastinal chest tube removal (placebo group = 20.6 hours; trial group = 19.8 hours)	No
Primary	Number of Units of Packed Red Blood Cells (PRBC) Transfused Following Coronary Artery Bypass Graft Surgery	Research participants were to receive a blood transfusion in the Intensive Care Unit (ICU) post-operatively if hemoglobin reached a nadir of 80g/L, or at the discretion of the intensivist or cardiac surgeon according to patient clinical status. Transfusion was quantified based on the number of units of PRBC received. (1 unit = 1 bag of blood, as prepared by Canadian Blood Services). Clinical status of research participants was followed throughout their duration in the ICU only. Participation in this study ended upon transfer out of the ICU, to the Cardiology Ward.	From ICU admission to transfer to the Cardiology Ward (placebo group = 24.4 hours; trial group = 24.7 hours)	No
Secondary	Volume of Blood Loss at 6 Hours	Volume of chest tube loss at 6 hours (assuming the total volume of loss is blood).	6 hours following admission to the Intensive Care Unit	No
Secondary	Volume of Blood Loss After 12 Hours	Volume of chest tube loss at 12 hours (assuming the total volume of loss is blood).	12 hours following admission to the Intensive Care Unit	No