DEPOSITION - Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery

Study Overview
=================
Brief Summary
-----------------
The aim is to conduct a double-dummy multi-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TxA) versus the usual intravenous TxA in patients undergoing on-pump cardiac surgery.

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 but to maintain the protection against bleeding. When TxA is used directly on the tissues (topically) for other type of surgeries (joints), TxA is effective to reduce blood loss and transfusions. The aim is to prove that direct application of TxA on the heart can eliminate postoperative seizures and reduce the amount of blood transfusions in patients who have cardiac surgery.

Official Title
-----------------
Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) Study

Conditions
-----------------
Bleeding, Surgical Blood Loss, Seizures

Intervention / Treatment
-----------------
* Drug: Tranexamic Acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age Undergoing a cardiac surgical procedure (i.e. isolated coronary artery bypass graft (CABG), isolated single cardiac valve surgery or a combination of both or isolated ascending aorta replacement) with the use of cardiopulmonary bypass (CPB) and median sternotomy Provide written informed consent Exclusion Criteria: Allergy to tranexamic acid Undergoing minimally invasive surgery Fulfill any of the following transfusion risk factors (A-D): A. Emergency surgery B. History of bleeding disorder C. Inherited thromboembolic or hemorrhagic disease D. Infective endocarditis (active) History of previous cardiac surgery Estimated glomerular filtration rate <30 mL/min (CKD-EPI equation) or on dialysis Pre-operative hemoglobin > 170 g/L or <110 g/L Pre-operative thrombocytopenia (<50,000 platelets per µL) Expected circulatory arrest Pregnancy or breast feeding Previously enrolled in the DEPOSITION trial Refusal of blood products Pericardiectomy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topical Tranexamic Acid/Placebo<br>Topical Tranexamic Acid 5g to 10g (50 to 100mL) or placebo. The topical will be poured into the pericardial and mediastinal cavities after protamine administration. | Drug: Tranexamic Acid<br>* Tranexamic Acid is a medication used to treat or prevent excessive blood loss from major trauma, post partum, surgery, tooth removal, nose bleeds, and heavy menstruation.<br>* Other names: Cyklokapron;|
| Active Comparator: Intravenous Tranexamic Acid/Placebo<br>Intravenous Tranexamic Acid 1 to 10g (10 to 100mL) or placebo administered intravenously at the induction of anesthesia as a bolus-infusion. | Drug: Tranexamic Acid<br>* Tranexamic Acid is a medication used to treat or prevent excessive blood loss from major trauma, post partum, surgery, tooth removal, nose bleeds, and heavy menstruation.<br>* Other names: Cyklokapron;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients experiencing an in-hospital seizure | To determine in patients undergoing on-pump cardiac surgery, if topical tranexamic acid (intra-pericardial) is superior to the usual intravenous tranexamic acid administration for reducing the risk of in-hospital seizure. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients in-hospital who receive red blood cell transfusions | To determine in patients undergoing on-pump cardiac surgery, if topical tranexamic acid (intra-pericardial) compared with intravenous tranexamic acid administration is associated with a non-inferior risk of in-hospital red blood cell transfusion. | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tranexamic Acid, On-pump Cardiac Surgery