Efficacy of Tranexamic Acid and Epsilon-aminocaproic Acid in Reducing Bleeding and Transfusions in Cardiac Surgery

Brief Summary
The investigators primary objective is to compare the effectiveness of epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) in reducing bleeding and transfusion in cardiac surgery, with the hypothesis that TA is more effective. The investigators also seek to further examine the clinical benefits and adverse effects profiles of epsilon-aminocaproic acid and tranexamic acid.
Brief Title
Efficacy of Tranexamic Acid and Epsilon-aminocaproic Acid in Reducing Bleeding and Transfusions in Cardiac Surgery
Detailed Description
This is a single center double blinded randomized controlled study comparing the effectiveness of epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) in reducing 24hour blood transfusion and chest tube drainage. From October 2008 to September 2011, patients greater than 18 years of age, scheduled for cardiac surgery requiring CPB were consented. Eligible operations included; coronary artery bypass graft surgery (CABG), a heart valve repair/replacement, or a concomitant CABG and valve surgery were enrolled.

Consented patients were randomized into one of the two groups using a 1:1 randomization sequence generated by a computer program. Randomization sequence and the study drugs were kept in a locked box and were opened only by unblinded study personnel who were not involved in the clinical care of the patient. This person prepared the study drug following the instructions of the study protocol, resulting in preparations of EACA and TA that contained equi-potent similar volumes of the drug in the syringe, in order to ensure blinding. Antifibrinolytic study drug was administered following anesthetic induction. EACA was administered as a bolus loading dose of 150 mg/ kg followed by a maintenance infusion of 15 mg/ kg /hr. TA was administered as a bolus dose of 30 mg /kg followed by a 16 mg/ kg/hour maintenance infusion. Maintenance infusion of both drugs was discontinued when the patient arrived in the cardiac surgical intensive care unit. In addition to routine blood sampling ( standard of care in the investigators hospital), patients had thromboelastogram(TEG) and D-dimer levels drawn at the following time points: post incision but prior to initial antifibrinolytic load, immediately following the antifibrinolytic loading dose, and post-protamine reversal of heparin.

The primary endpoint was the amount of chest tube drainage and the amount of blood products used in the first 24 hours following surgery (surrogate measurement for blood loss) was measured at 4, 8, 12 and 24 hours after surgery. The incidence of packed red blood cells (PRBC), fresh frozen plasma (FFP), cryoprecipitate and platelets administered during the first 24 hours after surgery was collected. Additionally, patients were monitored for any complications during their stay in the hospital and up to 30 days post-operatively. Complications included renal dysfunction (defined as the need for at least 1 hemodialysis or doubling of pre-surgical creatinine levels), stroke and seizures (clinically diagnosed), myocardial infarction (new Q waves in two electrocardiogram leads), cardiac arrest, respiratory failure, re-operation and death. Monitoring of the patients prior to discharge involved chart review during their stay in the hospital; if a post-operative complication was suspected, the complication was confirmed using Montefiore Medical Center's Carecast Database, which contained independent results such as MRI's, CT scans, or labs. Additionally, computer records of the patients were searched to determine if there were documented complications in the 30-day post-operative time period.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Bleeding
Eligibility Criteria
Inclusion Criteria:

* Informed consent obtained before any trial-related activities
* Subjects scheduled to undergo cardiac surgery requiring cardiopulmonary bypass

Exclusion Criteria:

* Vulnerable patient populations (unable to consent)
* Religious or other prohibitive reason for not receiving blood transfusion
* History of allergy to epsilon-aminocaproic acid or tranexamic acid
* Pregnant or breast-feeding (if applicable)
* The participation in another clinical or device trial that would affect the patient's coagulation profile
* Cardiac or cardiopulmonary transplantation procedure
* Any history of stroke and/or non-coronary thrombotic disorders (DVT, PE)
* Clinical signs consistent with non-coronary thrombotic disease
* Known congenital deficiency of Protein C, Protein S, Antithrombin and homozygous Factor V Leiden
* Known congenital bleeding disorders
* Weight \< 50 kg
* Weight \> 150 kg
* Acute renal failure or creatinine \> 2.0 mg/dL
* Current surgery including any implantable ventricular assist device requiring CPB including ECMO (extracorpeal membrane oxygenation)
* Current surgery including the aortic arch and/or descending thoracic aorta
* Any changes to the planned surgery, which result int he patient not requiring CPB or meeting exclusion criteria
Inclusion Criteria
Inclusion Criteria:

* Informed consent obtained before any trial-related activities
* Subjects scheduled to undergo cardiac surgery requiring cardiopulmonary bypass

Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02655653
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
08-08-291
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-blinded Trial Comparing the Efficacy of Tranexamic Acid and Epsilon-aminocaproic Acid in Reducing Bleeding and Transfusions in Cardiac Surgery
Primary Outcomes
Outcome Description
Chest tube drainage are collected from the nursing records, every 4th hourly the amount fluid collected is reported in the collection sheets.
Outcome Measure
Chest Tube Drainage
Outcome Time Frame
4 hours, 8 hours, 12 hours, 24 hours
Outcome Description
Four types of blood products may be given through blood transfusions: whole blood, red blood cells, platelets, and plasma
Outcome Measure
Median Amount of Blood Products Used
Outcome Time Frame
24 hours after surgery
Secondary Outcomes
Outcome Description
Confirmed diagnosis of renal dysfunction and hospitalization for the same within 30 days after the surgery
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Diagnosis of Renal Dysfunction Post-operation
Outcome Description
Confirmed diagnosis of myocardial infraction and hospitalization for the same within 30 days after the surgery
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Diagnosis of Myocardial Infarction Post-operation
Outcome Description
Confirmed diagnosis of respiratory arrest and hospitalization for the same within 30 days after the surgery
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Number of Participants Who Have Confirmed Diagnosis of Respiratory Arrest
Outcome Description
Confirmed diagnosis of stroke and hospitalization for the same within 30 days after the surgery
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Number of Participants With Confirmed Diagnosis of Stroke
Outcome Description
Confirmed diagnosis of seizure and hospitalization for the same within 30 days after the surgery
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Number of Participants With Confirmed Diagnosis of Seizure
Outcome Description
Confirmed diagnosis of reopeartion and hospitalization for the same within 30 days after the surgery
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Reoperation
Outcome Time Frame
Within 30 days after surgery
Outcome Measure
Mortality Within 30 Days Post-operation
Start Date
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jonathan Leff
Investigator Email
jleff@montefiore.org
Investigator Phone

Categories Mesh Debug
Blood Disorders --- HEMORRHAGE
MeSH Terms
HEMORRHAGE
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS