Tranexamic Acid, Hemorrhage and Transfusions After Combined Aortic Valve Replacement and Coronary Artery Bypass Surgery.

Phase 4 Study of Tranexamic Acid for Elderly Patients Undergoing Combined Aortic Valve Replacement and Coronary Artery Bypass Surgery.

In this study we will investigate whether tranexamic acid given as an intravenous bolus injection before start of surgery, followed by a continuous infusion during surgery reduces, perioperative hemostatic activation, and postoperative bleeding and the need for transfusions of blood components in elderly patients undergoing combined aortic valve replacement and coronary artery bypass surgery. Tranexamic acid will be compared with placebo (0.9% sodium chloride) in a randomized and double-blind study design.

The study hypothesis is that tranexamic acid will reduce hemostatic activation and postoperative hemorrhage and the need for blood component transfusions in this group of patients.

Study Overview

• Status: Completed
• Conditions: Hemorrhage
• Intervention / Treatment: Drug: Tranexamic acid; Drug: placebo

Detailed Description

It has previously been shown that elderly patients show signs of increased perioperative hemostatic activation after coronary artery bypass grafting. In particular, compared to younger patients, elderly patients had more extensive fibrinolysis postoperatively. The antifibrinolytic drug tranexamic acid has been shown to reduce fibrinolysis, bleeding, and the need for transfusions of blood components after various cardiac surgical procedures. In this study we will investigate whether tranexamic acid reduces perioperative activation of coagulation as measured by plasma concentrations of antithrombin, thrombin-antithrombin complex, and prothrombin fragment 1+2, whether tranexamic acid reduces perioperative fibrinolysis as measured by plasma concentrations of D-dimer, and whether tranexamic acid reduces platelet activation as measured by plasma concentrations of neutrophil activating peptide 2 and by flow cytometry in elderly (above 70 years of age) patients undergoing combined aortic valve replacement and coronary artery bypass surgery. The primary endpoint of the study will, however, be total postoperative bleeding and the need for transfusions of blood components during and after surgery. The need for transfusions will be registered during the whole hospital stay. Patients will be randomized into two groups and given either tranexamic acid or placebo (0.9% sodium chloride) as an intravenous bolus injection before start of surgery followed by an intravenous infusion during surgery. Blood samples for the above mentioned plasma concentration measurements will be drawn preoperatively, intraoperatively during CPB, and 30 minutes and 3, 5, and 20 hours postoperatively. Postoperative bleeding will be registered for 16 hours. The need for any transfusions of blood products will be registered for the whole hospital stay.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway, 7006
    • St. Olav University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Patients above 70 years of age scheduled for combined aortic valve replacement and coronary artery bypass surgery.

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Exclusion Criteria: Patients younger than 70 years of age. Patients scheduled for other procedures than combined aortic valve replacement and coronary artery bypass surgery. Patients who are not treated with aspirin. Patients with a medical condition known to influence the hemostatic system. Patients treated with drugs other than aspirin during the last week before surgery that may influence the hemostatic system, such as warfarin (coumarin), non-steroidal antiinflammatory drugs, clopidogrel, heparin, low molecular heparins. Patients who are treated with systemic steroids. Patients with a serum creatinin concentration above 140 micromol/l. Patients with an INR above 1.5. Patients who are not able to give written informed concent.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; 0.9% sodium chloride 10 mg/kg, as a bolus injection before surgery followed by 1 mg/kg/h as an infusion during surgery
Experimental: Tranexamic Acid	Drug: Tranexamic acid; Tranexamic acid 10 mg/kg as a bolus dose followed by an infusion of 1 mg/kg/hour. Bolus given before start of surgery, infusion continued during surgery.; Other Names: Cykokapron ACT: B02A A02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Transfusion of blood components	Intraoperatively and during postoperative stay

Secondary Outcome Measures

Outcome Measure	Time Frame
Postoperative hemorrhage	First 16 hours postoperatively
Fibrinolysis	20 hours postoperatively
Platelet activation	20 hours postoperatively
Activation of coagulation	20 hours postoperatively

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Investigators: Study Chair: Hilde Pleym, MD, PhD, St. Olavs Hospital; Principal Investigator: Guri Greiff, MD, St. Olavs Hospital; Principal Investigator: Alexander Wahba, MD, PhD, St. Olavs Hospital; Principal Investigator: Roar Stenseth, MD, PhD, St. Olavs Hospital

Publications and helpful links

General Publications

• Greiff G, Stenseth R, Wahba A, Videm V, Lydersen S, Irgens W, Bjella L, Pleym H. Tranexamic acid reduces blood transfusions in elderly patients undergoing combined aortic valve and coronary artery bypass graft surgery: a randomized controlled trial. J Cardiothorac Vasc Anesth. 2012 Apr;26(2):232-8. doi: 10.1053/j.jvca.2011.07.010. Epub 2011 Sep 15.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 12, 2006
• First Submitted That Met QC Criteria: September 12, 2006
• First Posted (Estimate): September 13, 2006

Study Record Updates

• Last Update Posted (Estimate): December 13, 2012
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Hemorrhage; Blood components; Transfusion; Platelet activation; Fibrinolysis
• 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: 4.2006.1285; 2006-004561-34 (EudraCT Number)