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

NCT01519245 | Completed Phase 3 Results

• 1 other identifier: 67452-01
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Coronary Artery Disease

Keywords

coronary artery bypass grafting; tranexamic acid; antifibrinolytic; administration, topical; operative blood salvage

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Secondary Outcomes (2)

• Volume of Blood Loss at 6 Hours

  6 hours following admission to the Intensive Care Unit

• Volume of Blood Loss After 12 Hours

  12 hours following admission to the Intensive Care Unit

Study Arms (2)

Trial Drug

EXPERIMENTAL

Solution containing 2 grams tranexamic acid + normal saline

Drug: Tranexamic Acid

Placebo

PLACEBO COMPARATOR

Normal saline

Drug: normal saline

Interventions

Tranexamic Acid DRUG

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.

Trial Drug

normal saline DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Saskatchewan: lead
• Saskatoon Health Region: collaborator

Related 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.

  PMID: 19247741 BACKGROUND

• 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.

  PMID: 16438759 BACKGROUND

• 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.

  PMID: 17218108 BACKGROUND

• 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.

  PMID: 10694619 BACKGROUND

• 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.

  PMID: 19538741 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Tranexamic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

* Small sample size * Low-risk CABG patients enrolled only * Break in protocol, with pre-pump TXA not given to 2 participants, and post-pump TXA given to 8 participants * Short study period, with no long-term follow-up data

Results Point of Contact

• Title: Dr. Kelsey Brose, Primary Investigator
• Organization: University of Saskatchewan

kelsey.brose@saskcancer.ca

306-655-1483

Study Officials

• Kelsey Brose, MD, FRCPC

  University of Saskatchewan, Department of Medicine, Division of Hematology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 26, 2012
• Study Start: December 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 2, 2013
• Results First Posted: July 2, 2013

Record last verified: 2013-05