Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid 2 Pilot Trial (DEPOSITION-2)

September 30, 2024 updated by: Hamilton Health Sciences Corporation

Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION)-2 Pilot Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Hamilton Health Sciences - General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: After CPB Tranexamic Acid/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).
Drug: After CPB Tranexamic Acid
Tranexamic acid 5 g (50 mL) administered after heparin reversal (i.e., after CPB).
Other Names:
  • Cyklokapron
Drug: Before CPB Placebo
Placebo (10 to 100 mL saline) administered intravenously at the induction of anesthesia as a bolus and/or continuous infusion.
Other Names:
  • Saline
Active Comparator: Before CPB Tranexamic Acid/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.
Drug: Before CPB Tranexamic Acid
Tranexamic acid 1 to 10 g (10 to 100 mL) administered intravenously as per standard care at the induction of anesthesia as a bolus and/or continuous infusion (i.e., before CPB).
Other Names:
  • Cyklokapron
Drug: After CPB Placebo
Placebo (50 mL saline) administered after heparin reversal.
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure the level of plasma TxA at 5 time points
Time Frame: 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.
From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points
Time Frame: 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.
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
Time Frame: 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.
From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility outcome (study-level): mean enrollment rate of the study
Time Frame: Start of enrollment (date of first patient) to end of enrollment (date of last patient).
Determine whether the mean enrolment rate of the trial (total number of patients recruited / total recruitment period in weeks) is 2 patients per week or more.
Start of enrollment (date of first patient) to end of enrollment (date of last patient).
Feasibility outcome (study-level): crossover rate of the study
Time Frame: Start of enrollment (date of first patient) to end of enrollment (date of last patient).
Determine whether the percentage of crossovers between groups (total number of patients with crossover / total number of patients recruited * 100) is less than 5%.
Start of enrollment (date of first patient) to end of enrollment (date of last patient).
Feasibility outcome (study-level): percentage of data completion of the study
Time Frame: Start of enrollment (date of first patient) to end of enrollment (date of last patient).
Determine whether the percentage of data completion (total number of patients with complete outcome data / total number of patients enrolled * 100) is more than 95%.
Start of enrollment (date of first patient) to end of enrollment (date of last patient).
Proportion of patients experiencing an in-hospital seizure
Time Frame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Appropriate descriptive statistics will be provided.
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Proportion of patients requiring any blood product transfusion
Time Frame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Appropriate descriptive statistics will be provided.
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Proportion of patients requiring re-operation for bleeding or cardiac tamponade
Time Frame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Appropriate descriptive statistics will be provided.
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Proportion of patients requiring a red blood cell transfusion
Time Frame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Appropriate descriptive statistics will be provided.
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Proportion of patients requiring pericardiocentesis
Time Frame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Appropriate descriptive statistics will be provided.
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Duration of intensive care unit stay
Time Frame: Number of hours in ICU are being collected at the Post-Operative Visit. Hour collection will start upon arrival at ICU post surgery and stop at ICU exit, up to 10 days maximum.
Appropriate descriptive statistics will be provided.
Number of hours in ICU are being collected at the Post-Operative Visit. Hour collection will start upon arrival at ICU post surgery and stop at ICU exit, up to 10 days maximum.
Proportion of patients experiencing the composite outcome of death, non-fatal myocardial infarction, or stroke
Time Frame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Appropriate descriptive statistics will be provided.
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hamilton Health Sciences Corporation

Investigators

  • Principal Investigator: Andre Lamy, MD, Hamilton General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2025

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

September 25, 2024

First Submitted That Met QC Criteria

September 30, 2024

First Posted (Actual)

October 2, 2024

Study Record Updates

Last Update Posted (Actual)

October 2, 2024

Last Update Submitted That Met QC Criteria

September 30, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DEPOSITION-2_2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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