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Bradykinin Receptor Antagonism During Cardiopulmonary Bypass (BRAC)
This study has been completed.
Sponsor:
Vanderbilt University
Information provided by (Responsible Party):
Mias Pretorius, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00223704
First received: September 19, 2005
Last updated: October 15, 2013
Last verified: October 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| Cardiopulmonary Bypass Inflammation Fibrinolysis Surgery | Drug: HOE 140 Drug: Aminocaproic Acid Drug: Placebo | Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | Bradykinin Receptor Antagonism During Cardiopulmonary Bypass |
Resource links provided by NLM:
Further study details as provided by Mias Pretorius, Vanderbilt University:
Primary Outcome Measures:
- Allogenic Blood Product Transfusion Risk [ Time Frame: Patients were followed for the duration of hospital stay, an average of 6 days ]Blood product transfusion during hospitalization that included packed red blood cells, plasma, platelets and cryoprecipitate.
Secondary Outcome Measures:
- Units of Packed Red Blood Cells Transfused During Hospitalization [ Time Frame: Patients were followed for the duration of hospital stay, an average of 6 days ]Units of Packed Red Blood Cells Transfused
- Units of Plasma Transfused During Hospitalization [ Time Frame: Patients were followed for the duration of hospital stay, an average of 6 days ]Units of plasma transfused
- Inflammatory Response as Measured by Interleukin-6 [ Time Frame: Patients were followed from the start of surgery until postoperative day 2 ]Interleukin-6 was measured at baseline, post-bypass and on postoperative day 1 and 2.
- Fibrinolytic Response as Measured by D-dimer [ Time Frame: Patients were followed from the start of surgery until postoperative day 1 ]D-dimer concentrations were measured at baseline, 30min and 60min of bypass, post-bypass and postoperative day 1
| Enrollment: | 150 |
| Study Start Date: | May 2006 |
| Study Completion Date: | June 2012 |
| Primary Completion Date: | June 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: HOE 140
Bradykinin receptor antagonist
|
Drug: HOE 140
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.
Other Name: Icatibant
|
|
Active Comparator: Aminocaproic Acid
Antifibrinolytic
|
Drug: Aminocaproic Acid
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.
Other Names:
|
|
Placebo Comparator: Placebo
Placebo
|
Drug: Placebo
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.
Other Name: Placebo/Normal Saline
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Subjects, 18 to 80 years of age, scheduled for elective CABG requiring CPB
- 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:
- Evidence of coagulopathy (INR greater than 1.7 without warfarin therapy)
- Preoperative hematocrit less than 30%
- Preoperative platelet count less than 100X109ml-1
- GPIIb/IIIa antagonist within 48 hours of surgery
- Emergency surgery
- Impaired renal function (serum creatinine >1.6 mg/dl)
- Pregnancy
- Breast-feeding
- 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
- History of alcohol or drug abuse
- Treatment with any investigational drug in the 1 month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00223704
Please refer to this study by its ClinicalTrials.gov identifier: NCT00223704
Locations
| United States, Tennessee | |
| TN Valley Healthcare System | |
| Nashville, Tennessee, United States, 37212 | |
| Vanderbilt University | |
| Nashville, Tennessee, United States, 37232 | |
Sponsors and Collaborators
Vanderbilt University
Investigators
| Principal Investigator: | Mias Pretorius, MBChB | Vanderbilt University |
More Information
Publications:
| Responsible Party: | Mias Pretorius, Associate Professor, Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT00223704 History of Changes |
| Other Study ID Numbers: |
IRB #051171 HL085740-02 |
| Study First Received: | September 19, 2005 |
| Results First Received: | July 29, 2013 |
| Last Updated: | October 15, 2013 |
Keywords provided by Mias Pretorius, Vanderbilt University:
|
Coronary Artery Bypass Blood Transfusion Bradykinin Receptor Antagonism Anti-Inflammatory Agents Antifibrinolytic Agents |
Additional relevant MeSH terms:
|
Inflammation Pathologic Processes Bradykinin Kininogens Aminocaproic Acid Antifibrinolytic Agents Icatibant Vasodilator Agents Cysteine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Fibrin Modulating Agents Hemostatics |
Coagulants Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Bradykinin B2 Receptor Antagonists Bradykinin Receptor Antagonists Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on September 19, 2017