Clinical trial NCT06622564: Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid 2 Pilot Trial
Official title: Decreasing Postoperative Blood Loss and Seizures by Timing of Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION)-2 Pilot Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Bleeding
Surgical Blood Loss
Seizures
Keywords: cardiac surgery
tranexamic acid
cardiopulmonary bypass
seizure
blood transfusion
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
First posted: 2024-10-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After CPB Tranexamic Acid + Before CPB Placebo versus Before CPB Tranexamic Acid + After CPB Placebo
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 (\&lt;50,000 platelets per µL) F. Pre-operative hemoglobin \&lt;110 g/L
3. Estimated glomerular filtration rate \&lt;30 mL/min (CKD-EPI equation) or on dialysis
4. Pre-operative hemoglobin \&gt;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

Primary outcomes:
measure: Measure the level of plasma TxA at 5 time points
timeFrame: From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.
Secondary outcomes:
measure: Measure the clot lysis time (i.e., fibrinolytic activity) at 5 time points
timeFrame: From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.
measure: Measure the plasmin generation (i.e., fibrinolytic activity) at 5 time points
timeFrame: From baseline to on arrival in the intensive care unit, 3 hours after arrival, 6 hours after arrival, and the next morning.
Other outcomes:
measure: Feasibility outcome (study-level): mean enrollment rate of the study
timeFrame: Start of enrollment (date of first patient) to end of enrollment (date of last patient).
measure: Feasibility outcome (study-level): crossover rate of the study
timeFrame: Start of enrollment (date of first patient) to end of enrollment (date of last patient).
measure: Feasibility outcome (study-level): percentage of data completion of the study
timeFrame: Start of enrollment (date of first patient) to end of enrollment (date of last patient).
measure: Proportion of patients experiencing an in-hospital seizure
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Proportion of patients requiring any blood product transfusion
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Proportion of patients requiring re-operation for bleeding or cardiac tamponade
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Proportion of patients requiring a red blood cell transfusion
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Proportion of patients requiring pericardiocentesis
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Duration of intensive care unit stay
timeFrame: 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.
measure: Proportion of patients experiencing the composite outcome of death, non-fatal myocardial infarction, or stroke
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - General Hospital
state: Ontario
Study officials:
affiliation: Hamilton General Hospital
name: Andre Lamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Habbab LM, Hussain S, Power P, Bashir S, Gao P, Semelhago L, VanHelder T, Parry D, Chu V, Lamy A. Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study. J Card Surg. 2019 May;34(5):305-311. doi: 10.1111/jocs.14027. Epub 2019 Mar 25.
citation: Lamy A, Sirota DA, Jacques F, Poostizadeh A, Noiseux N, Efremov S, Demers P, Akselrod B, Wang CY, Arora RC, Branny P, McGuinness SP, Brown CD, Jeanmart H, Zhao Q, Zhang H, Belley-Cote EP, Whitlock RP, Browne A, Copland I, Vincent J, Khatun R, Balasubramanian K, Bangdiwala SI, McGillion MH, Fox-Robichaud AE, Spence J, Yusuf S, Devereaux PJ; DEPOSITION Study Group. Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial. Circulation. 2024 Oct 22;150(17):1315-1323. doi: 10.1161/CIRCULATIONAHA.124.069606. Epub 2024 Apr 8.