Bradykinin Receptor Antagonism During Cardiopulmonary Bypass

• Status: Completed
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University; Vanderbilt University Medical Center
• Treatments: Aminocaproic Acid; Antifibrinolytic Agents; Bradykinin; Icatibant; Kininogens

Criteria

Inclusion Criteria:

1. Subjects, 18 to 80 years of age, scheduled for elective CABG requiring CPB

2. For female subjects, the following conditions must be met:

postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and willing to undergo urine beta-hcg testing prior to drug treatment and on every study day

Exclusion Criteria:

1. Evidence of coagulopathy (INR greater than 1.7 without warfarin therapy)

2. Preoperative hematocrit less than 30%

3. Preoperative platelet count less than 100X109ml-1

4. GPIIb/IIIa antagonist within 48 hours of surgery

5. Emergency surgery

6. Impaired renal function (serum creatinine >1.6 mg/dl)

7. Pregnancy

8. Breast-feeding

9. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult

10. History of alcohol or drug abuse

11. Treatment with any investigational drug in the 1 month preceding the study

12. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study

13. Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study