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

Phase 3

Completed

Conditions: Bleeding

Interventions: Drug: Tranexamic Acid administered
Drug: Epsilon-aminocaproic acid administered

Registration Number: NCT02655653

Lead Sponsor: Montefiore Medical Center

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 114

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tranexamic acid (TA)	Tranexamic Acid administered	Tranexamic Acid administered following induction: TA was administered as a bolus dose of 30 mg /kg followed by a 16 mg/ kg/hour maintenance infusion.
Epsilon-aminocaproic acid (EACA)	Epsilon-aminocaproic acid administered	Epsilon-aminocaproic acid 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.

Primary Outcome Measures

Name	Time	Method
Chest Tube Drainage	4 hours, 8 hours, 12 hours, 24 hours	Chest tube drainage are collected from the nursing records, every 4th hourly the amount fluid collected is reported in the collection sheets.
Median Amount of Blood Products Used	24 hours after surgery	Four types of blood products may be given through blood transfusions: whole blood, red blood cells, platelets, and plasma

Secondary Outcome Measures

Name	Time	Method
Diagnosis of Renal Dysfunction Post-operation	Within 30 days after surgery	Confirmed diagnosis of renal dysfunction and hospitalization for the same within 30 days after the surgery
Diagnosis of Myocardial Infarction Post-operation	Within 30 days after surgery	Confirmed diagnosis of myocardial infraction and hospitalization for the same within 30 days after the surgery
Number of Participants Who Have Confirmed Diagnosis of Respiratory Arrest	Within 30 days after surgery	Confirmed diagnosis of respiratory arrest and hospitalization for the same within 30 days after the surgery
Number of Participants With Confirmed Diagnosis of Stroke	Within 30 days after surgery	Confirmed diagnosis of stroke and hospitalization for the same within 30 days after the surgery
Number of Participants With Confirmed Diagnosis of Seizure	Within 30 days after surgery	Confirmed diagnosis of seizure and hospitalization for the same within 30 days after the surgery
Mortality Within 30 Days Post-operation	Within 30 days after surgery
Reoperation	Within 30 days after surgery	Confirmed diagnosis of reopeartion and hospitalization for the same within 30 days after the surgery