At a glance
ClinicalIndex Comparison Record- ✓Age 18 to 80 years scheduled for elective CABG requiring CPB
- ✕Evidence of coagulopathy (INR >1.7 without warfarin)
- ✕Preoperative hematocrit <30%
- ✕Preoperative platelet count <100×10^9/mL
- ✕GPIIb/IIIa antagonist within 48 hours of surgery
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Bradykinin Receptor Antagonism During Cardiopulmonary Bypass
In Brief
A Phase 3 clinical trial evaluating HOE 140, Aminocaproic Acid, and 1 other intervention for Cardiopulmonary Bypass and 3 related conditions. Completed, enrolled 150 participants across 2 sites.
Detailed Summary
Each year over a million patients worldwide undergo cardiac surgery requiring cardiopulmonary bypass (CPB). CPB is associated with significant morbidity including the transfusion of allogenic blood products, inflammation and hemodynamic instability. In fact, approximately 20% of all blood products transfused are associated with coronary artery bypass grafting procedures. Transfusion of allogenic blood products is associated with well-documented morbidity and increased mortality after cardiac surgery. Enhanced fibrinolysis contributes to increased blood product transfusion in the perioperative period. The current proposal tests the central hypothesis that endogenous bradykinin contributes to the hemodynamic, fibrinolytic and inflammatory response to CPB and that bradykinin receptor antagonism will reduce hypotension, inflammation and transfusion requirements. In SPECIFIC AIM 1 we will test the hypothesis that the fibrinolytic and inflammatory response to CPB differ during ACE inhibition and angiotensin II type 1 receptor antagonism. In SPECIFIC AIM 2 we will test the hypothesis that bradykinin B2 receptor antagonism attenuates the hemodynamic, fibrinolytic, and inflammatory response to CPB. In SPECIFIC AIM 3 we will test the hypothesis that bradykinin B2 receptor antagonism reduces the risk of allogenic blood product transfusion in patients undergoing CPB. These studies promise to provide important information regarding the effects of drugs that interrupt the RAS and generate new strategies to reduce morbidity in patients undergoing CPB.
Study Details
Timeline
Interventions
HOE 140 (a bradykinin B2 receptor antagonist) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. HOE 140 was given as an intravenous bolus of 22 µg/kg over one-half hour followed by an infusion of 18 µg/kg/hr.
Aminocaproic acid (an antifibrinolytic drug) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery. Aminocaproic acid was given as an intravenous bolus of 100 mg/kg over one-half hour followed by an infusion of 30 mg/kg/hr.
Normal saline (placebo) was started in the operating room after induction of anesthesia and before heparinization, continued throughout the bypass period, and discontinued at the end of surgery.