Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00405093 |
| Other study ID # |
0607008636 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
November 28, 2006 |
| Last updated |
January 17, 2017 |
| Start date |
July 2006 |
| Est. completion date |
May 2013 |
Study information
| Verified date |
January 2017 |
| Source |
Weill Medical College of Cornell University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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.
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.
