Clinical trial NCT00809393: Dose-ranging Study of Two Doses of Tranexamic Acid During Cardiac Surgery
Official title: Comparison of Two Tranexamic Acid Dose Regimens on Transfusion Needs During Cardiac Surgery With Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiopulmonary Bypass
Hemorrhage
Keywords: Antifibrinolytic
Tranexamic acid
Cardiopulmonary bypass
Transfusion
Hemorrhage
Lead sponsor: Hopital Foch
Sponsor class: OTHER
First posted: 2008-12-17
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: The primary study outcome is the number of patients in each group exposed to allogenic blood transfusion during the first 7 days after surgery.
timeFrame: 7th day
Secondary outcomes:
measure: 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.
timeFrame: 28th day
measure: Relationship between blood loss during the first 24 hours following the surgery and plasmatic concentration of acid tranexamic
timeFrame: 28 days
Other outcomes:
Locations:
city: Besancon
country: France
facility: department of anaesthesiology, CHU Jean Minjoz
city: Bordeaux
country: France
facility: department of anesthesiology, Haut Leveque Hospital
city: Paris
country: France
facility: department of anesthesiology, Bichat Hospital
city: Suresnes
country: France
facility: Hopital Foch
Study officials:
affiliation: Hopital Foch
name: Marc Fischler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grassin-Delyle S, Tremey B, Abe E, Fischler M, Alvarez JC, Devillier P, Urien S. Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Br J Anaesth. 2013 Dec;111(6):916-24. doi: 10.1093/bja/aet255. Epub 2013 Jul 23.