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

NCT00809393 | Completed Phase 4

• 1 other identifier: 2008/27
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 4

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. 1.Baseline
2. 2.5 min after the loading dose
3. 3.10 min after the beginning of bypass
4. 4.at the discontinuation of the infusion
5. 5.1 hour after the discontinuation Plasmatic dosage will be assessed using a high performance liquid chromatography technique.

Conditions

Cardiopulmonary Bypass; Hemorrhage

Keywords

Antifibrinolytic; Tranexamic acid; Cardiopulmonary bypass; Transfusion; Hemorrhage

Outcome Measures

Primary Outcomes (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.

  7th day

Secondary Outcomes (2)

• 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.

  28th day

• Relationship between blood loss during the first 24 hours following the surgery and plasmatic concentration of acid tranexamic

  28 days

Study Arms (2)

low dose

ACTIVE COMPARATOR

low dose tranexamic acid

Drug: tranexamic acid

high dose

EXPERIMENTAL

Drug: tranexamic acid

Interventions

tranexamic acid DRUG

10 mg/kg

low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hopital Foch: lead

Study Sites (4)

department of anaesthesiology, CHU Jean Minjoz

Besançon, 25030, France

Location

department of anesthesiology, Haut Leveque Hospital

Bordeaux, France

Location

department of anesthesiology, Bichat Hospital

Paris, 75018, France

Location

Hopital Foch

Suresnes, 92150, France

Location

Related Publications (1)

• 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.

  PMID: 23880099 DERIVED

MeSH Terms

Conditions

Hemorrhage

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Marc Fischler, MD

  Hopital Foch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2008
• First Posted: December 17, 2008
• Study Start: February 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: September 23, 2016

Record last verified: 2016-09

Locations

FR (4)