Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid 2 Pilot Trial

Phase 3

Not yet recruiting

• Conditions: Bleeding; Surgical Blood Loss; Seizures
• Interventions: Drug: After CPB Tranexamic Acid; Drug: Before CPB Tranexamic Acid; Drug: Before CPB Placebo; Drug: After CPB Placebo

• Registration Number: NCT06622564
• Lead Sponsor: Hamilton Health Sciences Corporation

Brief Summary

The goal of this clinical trial is to establish the feasibility of conducting a large trial to determine the optimal timing of intravenous tranexamic acid administration in cardiac surgery. The main questions it aims to answer are:

* Is it feasible to conduct a larger definitive trial?

* Can we measure the systemic tranexamic acid concentration and fibrinolytic potential in the blood samples?

Researchers will compare intravenous tranexamic acid administered before cardiopulmonary bypass versus after cardiopulmonary bypass to see if the systemic tranexamic acid concentration and fibrinolytic potential are similar or better.

Participants will:

* Provide written informed consent

* Receive tranexamic acid during surgery

* Provide blood samples at 5 time points: before surgery, on arrival in intensive care unit, 3 hours after arrival, 6 hours after arrival, and on the next morning.

Detailed Description

Postoperative bleeding related to open cardiac surgery increases the rates of complications and mortality. It results from the blood thinners that are needed for use. Intravenous tranexamic acid (TxA) has become a mainstay in cardiac surgical procedures for decreasing bleeding and minimizing transfusion requirements. Although intravenous TxA is usually well tolerated, there is a well-known risk (1 to 4%) of postoperative seizures. This is due to the similarity between TxA and the brain tissues. The aim is to eliminate the risk of seizures and to improve the protection against bleeding. When TxA is used before and during cardiopulmonary bypass (CPB), the presence of systemic TxA during de-airing of the heart and the termination of CPB may facilitate entry of TxA into the brain causing seizures. Administration of TxA after CPB may result in higher systemic concentrations that may be more effective for protecting against bleeding after surgery. The aim is to establish the feasibility of a definitive trial to prove that administration of TxA after CPB can eliminate postoperative seizures and reduce the amount of blood transfusions in patients who have cardiac surgery.

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-25
• Study First Submitted QC: 2024-09-30
• Last Update Submitted: 2024-09-30
• Study First Posted: 2024-10-02
• Last Update Posted: 2024-10-02
• Study Start: 2025-01-01
• Primary Completion: 2026-01-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. ≥18 years of age
2. Undergoing a cardiac surgical procedure (i.e., isolated CABG, isolated single cardiac valve surgery or a combination of both or isolated ascending aorta replacement) with the use of cardiopulmonary bypass
3. Provide written informed consent

Exclusion Criteria

1. Allergy to tranexamic acid

2. Fulfill any of the following transfusion risk factors (A-F):

   A. Emergency surgery B. History of bleeding disorder C. Inherited thromboembolic or hemorrhagic disease D. Infective endocarditis (active) E. Pre-operative thrombocytopenia (<50,000 platelets per µL) F. Pre-operative hemoglobin <110 g/L

3. Estimated glomerular filtration rate <30 mL/min (CKD-EPI equation) or on dialysis

4. Pre-operative hemoglobin >170 g/L

5. Expected circulatory arrest

6. Pregnancy or breast feeding

7. Previous enrollment in DEPOSITION trial

8. Refusal of blood products (e.g., Jehovah's Witnesses)

9. Isolated Pericardiectomy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
After CPB Tranexamic Acid/Placebo	After CPB Tranexamic Acid	In the intervention group, patients will receive intravenous administration (10-100 mL of saline placebo) at the induction of anesthesia as a bolus and/or continuous infusion. In addition, patients will receive intravenous administration (5 g of TxA) after heparin reversal (i.e., after CPB).
After CPB Tranexamic Acid/Placebo	Before CPB Placebo	In the intervention group, patients will receive intravenous administration (10-100 mL of saline placebo) at the induction of anesthesia as a bolus and/or continuous infusion. In addition, patients will receive intravenous administration (5 g of TxA) after heparin reversal (i.e., after CPB).
Before CPB Tranexamic Acid/Placebo	Before CPB Tranexamic Acid	In the control group, patients will receive an intravenous administration (1-10 g of TxA) at the induction of anesthesia as a bolus and/or continuous infusion (i.e., before CPB). In addition, patients will receive an intravenous administration (50 mL of saline placebo) after heparin reversal.
Before CPB Tranexamic Acid/Placebo	After CPB Placebo	In the control group, patients will receive an intravenous administration (1-10 g of TxA) at the induction of anesthesia as a bolus and/or continuous infusion (i.e., before CPB). In addition, patients will receive an intravenous administration (50 mL of saline placebo) after heparin reversal.

Primary Outcome Measures

Name	Time	Method
Measure the level of plasma TxA at 5 time points	From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.	Measure the level of plasma TxA at 5 time points: pre-operative, on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.

Secondary Outcome Measures

Name	Time	Method
Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points	From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.	Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points: pre-operative baseline, on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.
Measure the plasmin generation (i.e., fibrinolytic activity) at 5 time points	From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.	Measure the plasmin generation (i.e., fibrinolytic activity) at 5 time points: pre-operative baseline, on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.

Trial Locations

Locations (1)

Hamilton Health Sciences - General Hospital; 🇨🇦 Hamilton, Ontario, Canada