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

This study has been completed.
Sponsor:
Information provided by:
Hopital Foch
ClinicalTrials.gov Identifier:
NCT00809393
First received: December 15, 2008
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

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 Intervention Phase
Cardiopulmonary Bypass
Hemorrhage
Drug: tranexamic acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Two Tranexamic Acid Dose Regimens on Transfusion Needs During Cardiac Surgery With Cardiopulmonary Bypass

Resource links provided by NLM:


Further study details as provided by Hopital Foch:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Relationship between blood loss during the first 24 hours following the surgery and plasmatic concentration of acid tranexamic [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: February 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: low dose
low dose tranexamic acid
Drug: tranexamic acid
10 mg/kg
Experimental: high dose Drug: tranexamic acid
30 mg/kg

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809393

Locations
France
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
Investigators
Principal Investigator: Marc Fischler, MD Hopital Foch
  More Information

No publications provided by Hopital Foch

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pr marc Fischler, Hopital Foch
ClinicalTrials.gov Identifier: NCT00809393     History of Changes
Other Study ID Numbers: 2008/27
Study First Received: December 15, 2008
Last Updated: January 27, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hopital Foch:
Antifibrinolytic
Tranexamic acid
Cardiopulmonary bypass
Transfusion
Hemorrhage

Additional relevant MeSH terms:
Hemorrhage
Pathologic Processes
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014