Dose-ranging Study of Two Doses of Tranexamic Acid During Cardiac Surgery (Exacylcardio)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00809393
Recruitment Status : Completed
First Posted : December 17, 2008
Last Update Posted : September 23, 2016
Information provided by (Responsible Party):
Hopital Foch

Brief Summary:

Cardiac surgery with CardioPulmonary Bypass (CPB) exposes to per and postoperative bleeding, and may lead to allogenic blood transfusion re-intervention and many adverse outcomes. Prophylactic use of tranexamic Acid (TA) has been shown to decrease blood loss and blood transfusion during cardiac surgery.There currently are multiple dosing regimens for TA for cardiac surgery.Preliminary dose-response study has shown that low prophylactic dose of TA would be as accurate for haemostatic efficacy as higher dose.

The primary objective of this tri-center, prospective, double-blinded, randomised trial is to compare two administrations and dosing regimens of TA during cardiac surgery with CPB on the perioperative blood loss.

In addition to the clinical study, a pharmacokinétic/pharmacodynamic study will be conducted.

Patients are divided in two groups: low and high risk surgery. Methods: After written informed consent, patients are randomly assigned to one of the two treatment groups. The low dose TA group is: 10 mg/kg TA given over 15 min, followed by an infusion of 1 mg/kg/h throughout the operation, and 1 mg/kg into the CPB prime volume. The high dose group is :30 mg/kg TA given over 15 min, followed by an infusion of 16 mg/kg/h throughout the operation, and 2 mg/kg into the CPB prime volume. Hemodynamic and anaesthesia care will be as usual. A blood salvage device will be systematically used. The triggers for transfusion will be: red blood cells: haemoglobin less than 8 g/dl or 6 g/dl during CBP; Plasma: PT less than 50% or INR more than 1.5; platelets: platelets count less than 50/70 G/mm3; fibrinogen: fibrinogen less than 1g/l . All patients will receive standard anaesthesia and perioperative care.

In 60 consecutive patients in the principal investigator center, 5 blood samples will allow to assess the plasmatic concentration of tranexamic acid at different time of the surgery procedure:

  1. Baseline
  2. 5 min after the loading dose
  3. 10 min after the beginning of bypass
  4. at the discontinuation of the infusion
  5. 1 hour after the discontinuation Plasmatic dosage will be assessed using a high performance liquid chromatography technique.

Patients will be stratified in two groups for the statistical analysis; low and high risk surgery. Analysis will be in intention to treat. 300 patients should be recruited in each group to detect an absolute difference of respectively 10% (low risk cardiac surgery) and 20% (high risk cardiac surgery) in the number of patients exposed to allogenic blood transfusion between patients receiving high dose TA regimen and those receiving low dose TA regimen, assuming a power of 80% and a two-tailed value less than 0.05.

Condition or disease Intervention/treatment Phase
Cardiopulmonary Bypass Hemorrhage Drug: tranexamic acid Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Two Tranexamic Acid Dose Regimens on Transfusion Needs During Cardiac Surgery With Cardiopulmonary Bypass
Study Start Date : February 2009
Primary Completion Date : January 2011
Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: low dose
low dose tranexamic acid
Drug: tranexamic acid
10 mg/kg
Experimental: high dose Drug: tranexamic acid
30 mg/kg

Primary Outcome Measures :
  1. The primary study outcome is the number of patients in each group exposed to allogenic blood transfusion during the first 7 days after surgery. [ Time Frame: 7th day ]

Secondary Outcome Measures :
  1. Number of fresh plasma frozen units, platelets units needed for the 7 days , post operative blood loss in the 24 hours, needed or repeat surgery due to haemorrhage for the 24 hours following surgery, in-hospital death at 7 and 28 days. [ Time Frame: 28th day ]
  2. Relationship between blood loss during the first 24 hours following the surgery and plasmatic concentration of acid tranexamic [ Time Frame: 28 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Any type of cardiac surgical procedure requiring CPB (including coronary artery bypass grafting, valve repair or replacement, aortic surgery, endocarditis).

Exclusion Criteria:

  • Emergency surgery, age < 18 years old, pregnancy, history of allergy to TA, history of seizure or thromboembolism event, history of previous antifibrinolytic or thrombolytic therapy within 5 days of surgery, coagulation disorder, liver disease, renal failure (clearance < 30 ml/min), Jehovah witness.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00809393

department of anaesthesiology, CHU Jean Minjoz
Besancon, France, 25030
department of anesthesiology, Haut Leveque Hospital
Bordeaux, France
department of anesthesiology, Bichat Hospital
Paris, France, 75018
Hopital Foch
Suresnes, France, 92150
Sponsors and Collaborators
Hopital Foch
Principal Investigator: Marc Fischler, MD Hopital Foch

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Hopital Foch Identifier: NCT00809393     History of Changes
Other Study ID Numbers: 2008/27
First Posted: December 17, 2008    Key Record Dates
Last Update Posted: September 23, 2016
Last Verified: September 2016

Keywords provided by Hopital Foch:
Tranexamic acid
Cardiopulmonary bypass

Additional relevant MeSH terms:
Pathologic Processes
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action