Clinical trial NCT02655653: Efficacy of Tranexamic Acid and Epsilon-aminocaproic Acid in Reducing Bleeding and Transfusions in Cardiac Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bleeding
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2016-01-14
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Chest Tube Drainage
timeFrame: 4 hours, 8 hours, 12 hours, 24 hours
measure: Median Amount of Blood Products Used
timeFrame: 24 hours after surgery
Secondary outcomes:
measure: Diagnosis of Renal Dysfunction Post-operation
timeFrame: Within 30 days after surgery
measure: Diagnosis of Myocardial Infarction Post-operation
timeFrame: Within 30 days after surgery
measure: Number of Participants Who Have Confirmed Diagnosis of Respiratory Arrest
timeFrame: Within 30 days after surgery
measure: Number of Participants With Confirmed Diagnosis of Stroke
timeFrame: Within 30 days after surgery
measure: Number of Participants With Confirmed Diagnosis of Seizure
timeFrame: Within 30 days after surgery
measure: Reoperation
timeFrame: Within 30 days after surgery
measure: Mortality Within 30 Days Post-operation
timeFrame: Within 30 days after surgery
Other outcomes:
measure: Patient Demographics
timeFrame: Baseline
measure: Type of Surgery
timeFrame: Intraoperative
measure: Intraoperative Characteristics
timeFrame: Intraoperative
Locations:
Study officials:
affiliation: Montefiore Medical Center
name: Jonathan D Leff, MD
role: PRINCIPAL_INVESTIGATOR
References: