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Bradykinin Receptor Antagonism During Cardiopulmonary Bypass (BRAC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mias Pretorius, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00223704
First received: September 19, 2005
Last updated: February 15, 2013
Last verified: February 2013
History of Changes
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Bradykinin Receptor Antagonism During Cardiopulmonary Bypass

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Allogenic blood product transfusion risk. [ Time Frame: Hospitilization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of transfusions in patients exposed to blood products [ Time Frame: Hospitilization ] [ Designated as safety issue: No ]
  • Inflammatory Response [ Time Frame: Hospitilization ] [ Designated as safety issue: No ]
    Inflammatory response as measured by IL-6, IL-8 and IL-10

  • Fibrinolytic response [ Time Frame: Hospitilization ] [ Designated as safety issue: Yes ]
    PAI-1 and t-PA antigen will be measured

  • Oxidative stress response [ Time Frame: Hospitilization ] [ Designated as safety issue: Yes ]
    Plasma F2isoP and isoF will be measured


Enrollment: 151
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
Bradykinin receptor antagonist administered prior to CPB
Other Name: Icatibant
Active Comparator: Aminocaproic Acid
Antifibrinolytic
 Drug: Aminocaproic Acid
Amionocaproic acid administered prior to CPB
Other Name: Amicar
Placebo Comparator: Placebo
Placebo
 Drug: Placebo
Placebo
Other Name: Placebo/Normal Saline

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00223704

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
TN Valley Healthcare System
Nashville, Tennessee, United States, 37212
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
Last Updated: February 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Coronary Artery Bypass
Blood Transfusion
Bradykinin Receptor Antagonism
Anti-Inflammatory Agents
Antifibrinolytic Agents

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
6-Aminocaproic Acid
Antifibrinolytic Agents
Icatibant
Anti-Inflammatory Agents
Bradykinin
Kininogens
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
 Vasodilator Agents
Cardiovascular Agents
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents

ClinicalTrials.gov processed this record on May 16, 2013