Aprotinin Use and Renal Outcome in Hypothermic Bypass and Circulatory Arrest for Surgical Repair of Thoracic Aorta.

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Weill Medical College of Cornell University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00405093
First received: November 28, 2006
Last updated: March 7, 2012
Last verified: September 2010
  Purpose

Primary Objective: The aim of this study is to assess the effects of Aprotinin (an antifibrinolytic drug used to reduce bleeding during cardiac surgery) on renal function in patients undergoing surgery with use of hypothermic bypass and circulatory arrest for repair of the thoracic aorta.

Secondary Objective: To compare the effects of Aprotinin and Amicar on major vascular outcomes following thoracic aorta surgery with use of hypothermic bypass and circulatory arrest.


Condition
Circulatory Arrest

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Aprotinin Use and Renal Outcome in Hypothermic Bypass and Circulatory Arrest for Surgical Repair of Thoracic Aorta. A Retrospective Study.

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Estimated Enrollment: 2000
Study Start Date: July 2006
Estimated Study Completion Date: September 2012
  Hide Detailed Description

Detailed Description:

Significance:

Complex surgery of the ascending thoracic aorta and the aortic arch requires use of cardiopulmonary bypass (CPB) with moderate or profound total body hypothermia and circulatory arrest. As expected, coagulation disorder can be common and severe requiring multiple transfusions of blood product, which, in turn, is associated with increased risk of morbidity and mortality. Over the years, many techniques have been employed to ameliorate CPB- related bleeding with some agents such as aprotinin proving to be efficacious but centered in controversy either because of high cost or due to safety concerns.

Aprotinin is a serine protease inhibitor, intended to limit blood loss in patients undergoing surgery, was approved for use 13 years ago, and now administered in more than 250,000 surgery patients per year. Although its mechanism of action is not entirely known, it is shown to interfere with contact activation, preserve platelet function, inhibit fibrinolysis, and having some anti-inflammatory effects. Multiple studies have shown its superiority for reducing blood loss over other antifibrinolytics while other studies showing safety concerns regarding early graft closure causing myocardial infarction (following coronary bypass surgery), renal failure, vascular thrombosis, and death. Of note, several other studies have addressed such safety concerns- finding that the risk of the aforementioned vascular complications are comparable to results utilizing placebo or other antifibrinolytics such as aminocaproic acid. For example, the associated renal dysfunction was attributed to a competitive excretion process involving creatinine. That is, aprotinin competes with creatinine for elimination by the kidneys such that the apparent renal dysfunction is transient and a false marker of renal injury. However, the issue of renal injury has recently re-emerged as a serious problem in a multicenter study on patients undergoing coronary revascularization, whereby more than two fold increase in postoperative renal dysfunction as well as a nearly two fold rise in postoperative stroke was reported.

Much of the controversy and many of the conflicting results arise from either inadequate information (i.e., the definitive prospective study has not been done), from inadequately powered studies for the intended outcome, inclusion of multi-institution and multi-surgeon outcomes, or from studies involving patients with advanced ischemic heart disease whose ventricular function may have been compromised perioperatively. To overcome the mentioned limitations, and to better characterize to postoperative renal outcomes, we propose to investigate the safety of aprotinin in a single institution, single surgeon, and very large homogenous surgical cohort who underwent surgical repair of the ascending and aortic arch with use of hypothermic CPB.

Methods:

This will be a retrospective review of data collected between 1998 and present (nearly 900 patients) on adult patients having had ascending aorta and or aortic arch surgery at the NewYork Presbyterian Hospital. Data on demographics, preoperative, intraoperative, and postoperative clinical events will be extracted from the patient's electronic record and recorded on a database (Variables to be collected are presented in Appendix 1). A renal event will be comprised of renal dysfunction; defined by a serum creatinine level of at least 2.0 mg/dL (177 µmol/L), accompanied by an increase of at least 0.70 mg/dL (62 µmol/L) from baseline or renal failure; defined need for renal replacement therapy. Creatinine values and creatinine clearance will be recorded/calculated preoperatively and postoperatively until hospital discharge.

Statistical Analysis Include analysis for association between potential preoperative, intraoperative, and early postoperative variables with postoperative renal dysfunction by univariate analysis (student's t test and Fisher's exact test). The variables identified by univariate testing (p< 0.15) will be entered into a multivariate logistic regression. Significance will be set a P < 0.05 and odds ratio will be calculated where applicable.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult male and female patients having surgery of ascending and aortic arch with the use of Antifibrinolytic agents (Aprotinin and Aminocaproic Acid)

Criteria

Inclusion Criteria:

  1. Adult male and female patients having surgery of ascending and aortic arch
  2. Use of Antifibrinolytic agents (Aprotinin and Aminocaproic Acid)

Exclusion Criteria:

  1. Emergency surgery for ruptured aorta
  2. Pre-Existing Renal Failure or Renal dysfunction (creatinine >2.0 mg/dl)
  3. Moderate or Severe Ventricular Dysfunction
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405093

Contacts
Contact: James Osorio, MD 212-746-0392 jao2002@med.cornell.edu

Locations
United States, New York
The New York Presbyterian Hospital - Weill Medical College of Cornell University Recruiting
New York, New York, United States, 10021
Contact: James Osorio, MD    212-746-0392    jao2002@med.cornell.edu   
Principal Investigator: James Osorio, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: James Osorio, MD Associate Professor
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00405093     History of Changes
Other Study ID Numbers: 0607008636
Study First Received: November 28, 2006
Last Updated: March 7, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
cardiopulmonary bypass
circulatory arrest
aprotinin
thoracic aorta surgery

Additional relevant MeSH terms:
Heart Arrest
Cardiovascular Diseases
Heart Diseases
Aprotinin
Coagulants
Enzyme Inhibitors
Hematologic Agents
Hemostatics
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Therapeutic Uses
Trypsin Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014