Bleeding, Seizures, Surgical Blood Loss
Conditions
Keywords
Tranexamic Acid, On-pump Cardiac Surgery
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.
Interventions
DRUGTranexamic Acid
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.
Sponsors
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The pharmacy will prepare 2 syringes of 50 ml of topical TxA (5 g) or placebo. They will also prepare for the same patient 2 syringes of 50 ml (5 g) for intravenous (i.v.) injection or placebo. TxA is similar in all aspects to normal saline. Blinding of both teams will be easy. The syringes will be prepared and randomized in pharmacy before the surgery.
Intervention model description
Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥ 18 years of age 2. 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 3. Provide written informed consent
Exclusion criteria
1. Allergy to tranexamic acid 2. Undergoing minimally invasive surgery 3. 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) 4. History of previous cardiac surgery 5. Estimated glomerular filtration rate \<30 mL/min (CKD-EPI equation) or on dialysis 6. Pre-operative hemoglobin \> 170 g/L or \<110 g/L 7. Pre-operative thrombocytopenia (\<50,000 platelets per µL) 8. Expected circulatory arrest 9. Pregnancy or breast feeding 10. Previously enrolled in the DEPOSITION trial 11. Refusal of blood products 12. Pericardiectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients experiencing an in-hospital seizure | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients in-hospital who receive red blood cell transfusions | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood product transfusions | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Analyzed using an ANCOVA model. In such a model, bags of blood product will be included as a dependent variable, whereas dose of tranexamic acid and treatment will be included as covariates. |
| Re-operation for bleeding or tamponade | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | Analyzed with a binomial regression |
| Duration of ICU stay | 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. | Analyzed using an ANCOVA model. |
| MACE (Death, non-fatal Myocardial Infarction (MI), or non-fatal stroke) | Start of surgery to hospital discharge or 10 days maximum (whichever occurs first) | A Cox proportional hazard model will be used to analyze the time to the first occurrence of the composite of death, non-fatal MI, or non-fatal stroke (MACE). |
Countries
Canada, China, Czechia, Malaysia, New Zealand, Russia
Outcome results
None listed