Bleeding, Surgical Blood Loss
Conditions
Keywords
Tranexamic Acid, Cardiac surgery
Brief summary
The aim is to conduct a double-blinded single-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TA) versus the usual intravenous TA in patients undergoing cardiac surgery at the Hamilton General Hospital. This pilot study will assess the feasibility to perform a large randomized international trial exploring this objective.
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 (TA) has become a mainstay in cardiac surgical procedures for decreasing bleeding and minimizing transfusion requirements. Although intravenous TA is usually well tolerated, there is a well-known risk (1 to 4%) of postoperative seizures. This is due to the similarity between TA and the brain tissues. The aim is to eliminate the risk of seizures but to maintain the protection against bleeding. When TA is used directly on the tissues (topically) for other type of surgeries (joints), TA is effective to reduce blood loss and transfusions. The aim is to prove that direct application of TA 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 1 syringe of 50 ml of topical TA (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. TA 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
* Male or female \>= 18 years old * Undergoing cardiac surgical procedure with the use of cardiopulmonary bypass and median sternotomy * Provide written informed consent
Exclusion criteria
* Poor (English) language comprehension * Minimally invasive valve surgery * Off-pump procedures * Emergency operations * Known history of increased bleeding disorder * Thromboembolic disease * Allergy to tranexamic acid * Severe renal impairment (eGFR \<30 mL/min/1.73m2 )
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Volume of Mediastinal Fluid Collected From Participants | Fluid collected in the first 24 hours after the surgical procedure | Cumulative volume (mL) of fluid collected from mediastinal drainage tubes 24 hours after the surgical procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mortality | Patients will be followed post-operatively until hospital discharge | The occurrence of death due to any cause |
| Number of Participants With RBC Transfusion | Intra-operative and post-operative RBC transfusions | Patients requiring a red blood cell transfusion |
| Number of Participants With Seizures | Patients will be followed post-operatively until hospital discharge | Patients experiencing a post-operative seizure |
| Median Number of Hours Participants Spent in ICU | Number of hours spent in ICU from arrival to exit (collected at the Post-Operative Visit). | Number of hours participants spent in the intensive care unit (ICU) |
| Mean Concentration of TxA in Plasma Collected From Participants | on arrival in ICU within 3 hours | Plasma TxA concentrations measured from blood samples taken upon arrival in the ICU |
| Number of Participants With Re-operation for Bleeding or Tamponade | Patients will be followed post-operatively until hospital discharge | Occurrence of re-operation for the purpose of bleeding or cardiac tamponade |
Countries
Canada
Participant flow
Recruitment details
Between December 2017 and April 2018 a total of 97 patients were randomized to the topical (n = 49) and intravenous (n = 48) groups.
Participants by arm
| Arm | Count |
|---|---|
| Topical TxA (Intervention) 50 mL of topical tranexamic acid (equivalent to 5 g TxA) poured into the pericardial and mediastinal cavities in 2 equal doses: 25 mL when the patient comes off-pump and the remaining 25 mL before sternotomy closure. In addition, patients will receive intravenous placebo (saline) administered as per anesthetist standard of care. | 49 |
| Intravenous TxA (Control) Up to 100 mL of intravenous tranexamic acid (equivalent to 10 g TxA) administered as per anesthetist standard of care. In addition, patients will receive topical placebo (saline) poured into the pericardial and mediastinal cavities in 2 equal doses: 25 mL when the patient comes off-pump and the remaining 25 mL before sternotomy closure. | 48 |
| Total | 97 |
Baseline characteristics
| Characteristic | Total | Topical TxA (Intervention) | Intravenous TxA (Control) |
|---|---|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 9.2 | 67.3 years STANDARD_DEVIATION 9.4 | 67.8 years STANDARD_DEVIATION 9.2 |
| Aspirin | 80 Participants | 38 Participants | 42 Participants |
| Carotid endarterectomy/stent | 4 Participants | 3 Participants | 1 Participants |
| Clopidogrel (Plavix) | 19 Participants | 12 Participants | 7 Participants |
| Diabetes mellitus | 38 Participants | 17 Participants | 21 Participants |
| History of seizures | 1 Participants | 1 Participants | 0 Participants |
| New oral anticoagulants (NOAC) | 7 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Aboriginal/Native Persons | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Southeast Asian/Malaysian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 92 Participants | 46 Participants | 46 Participants |
| Region of Enrollment Canada | 97 participants | 49 participants | 48 participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 86 Participants | 44 Participants | 42 Participants |
| Stroke | 6 Participants | 3 Participants | 3 Participants |
| Ticagrelor | 8 Participants | 3 Participants | 5 Participants |
| Transient ischemic attack | 4 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 49 | 1 / 48 |
| other Total, other adverse events | 0 / 49 | 0 / 48 |
| serious Total, serious adverse events | 0 / 49 | 0 / 48 |
Outcome results
Primary
Median Volume of Mediastinal Fluid Collected From Participants
Cumulative volume (mL) of fluid collected from mediastinal drainage tubes 24 hours after the surgical procedure
Time frame: Fluid collected in the first 24 hours after the surgical procedure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Topical TxA (Intervention) | Median Volume of Mediastinal Fluid Collected From Participants | 500 mL |
| Intravenous TxA (Control) | Median Volume of Mediastinal Fluid Collected From Participants | 540 mL |
Secondary
Mean Concentration of TxA in Plasma Collected From Participants
Plasma TxA concentrations measured from blood samples taken upon arrival in the ICU
Time frame: on arrival in ICU within 3 hours
Population: 4 patients from the topical TxA group and 3 patients from the intravenous TxA group were excluded because they either did not receive a TxA dose or received an incomplete TxA dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topical TxA (Intervention) | Mean Concentration of TxA in Plasma Collected From Participants | 0.58 microgram per milliliter per kilogram | Standard Deviation 0.41 |
| Intravenous TxA (Control) | Mean Concentration of TxA in Plasma Collected From Participants | 1.10 microgram per milliliter per kilogram | Standard Deviation 0.52 |
Secondary
Median Number of Hours Participants Spent in ICU
Number of hours participants spent in the intensive care unit (ICU)
Time frame: Number of hours spent in ICU from arrival to exit (collected at the Post-Operative Visit).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Topical TxA (Intervention) | Median Number of Hours Participants Spent in ICU | 23 hours |
| Intravenous TxA (Control) | Median Number of Hours Participants Spent in ICU | 26 hours |
Secondary
Number of Participants With Mortality
The occurrence of death due to any cause
Time frame: Patients will be followed post-operatively until hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical TxA (Intervention) | Number of Participants With Mortality | 1 Participants |
| Intravenous TxA (Control) | Number of Participants With Mortality | 1 Participants |
Secondary
Number of Participants With RBC Transfusion
Patients requiring a red blood cell transfusion
Time frame: Intra-operative and post-operative RBC transfusions
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical TxA (Intervention) | Number of Participants With RBC Transfusion | 19 Participants |
| Intravenous TxA (Control) | Number of Participants With RBC Transfusion | 23 Participants |
Secondary
Number of Participants With Re-operation for Bleeding or Tamponade
Occurrence of re-operation for the purpose of bleeding or cardiac tamponade
Time frame: Patients will be followed post-operatively until hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical TxA (Intervention) | Number of Participants With Re-operation for Bleeding or Tamponade | 0 Participants |
| Intravenous TxA (Control) | Number of Participants With Re-operation for Bleeding or Tamponade | 1 Participants |
Secondary
Number of Participants With Seizures
Patients experiencing a post-operative seizure
Time frame: Patients will be followed post-operatively until hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical TxA (Intervention) | Number of Participants With Seizures | 0 Participants |
| Intravenous TxA (Control) | Number of Participants With Seizures | 1 Participants |