Ignite Creation Date:
2024-05-05 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00156520
Status:
COMPLETED
Last Update Posted:
2010-04-12
First Post:
2005-09-08
Brief Title:
Platelet Function And Aggregometry In Patients With Aortic Valve Stenosis
Sponsor:
University of Rochester
Organization:
University of Rochester
Study Overview
Official Title:
Jeanne Grace Head Research Subjects Review Board
Status:
COMPLETED
Status Verified Date:
2010-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
It is known that patients with aortic stenosis including those undergoing cardiac surgery for this problem are prone to developing bleeding problems particularly of the gastrointestinal tract It is believed that the shear stress associated with blood flow through the abnormal aortic valve results in abnormal hemostasis Abnormalities include increased proteolysis of the von Willebrand factor vWF and increased binding of the high molecular weight multimers of vWF to platelet membranes with subsequent inappropriate platelet aggregation Thus appropriate aggregation of circulating platelets is impaired Cardiac surgery is associated with significant alterations in hemostasis Patients undergoing cardiac surgery consume a significant percent of available blood products throughout the United States and are subjected to various and numerous risks associated with blood product transfusion In addition excessive postoperative bleeding is a common cause for the need to surgically re-explore the chest cavity in patients who have just undergone cardiac surgical procedures Such additional surgery carries further cost and risk Following surgical correction of aortic valve stenotic pathology associated vWF abnormalities appear to reverse However this process can take several days Although all cardiac surgical patients are at risk for postoperative bleeding patients undergoing aortic valve surgery for aortic stenosis may be particularly at risk for this postoperative complication In addition patients with aortic valve stenosis who undergo noncardiac surgery may have a predisposition to bleeding because of similar underlying shear stress induced abnormal vWF and platelet function The proposed study is a trial to evaluate the effectiveness of 2 different antifibrinolytic drugs in ameliorating the hemostatic defect associated with aortic stenosis Aprotonin an antifibrinolytic agent which also has platelet preserving actions4 will be compared to the currently used anti-fibrinolytic epsilon aminocaproic acid EACA
Detailed Description:
Study subjects will be competent adult patients who are scheduled to undergo elective aortic valve surgery for severe aortic stenosis The process of informed consent will begin prior to the day of surgery either during a patients preoperative surgery clinic visit with one of the cardiac surgeons for any patient having such a clinic visit or during the preoperative anesthesia evaluation prior to the day of surgery At one or both of these times patients will be told of the study and given a copy of the informed consent for their reading An opportunity for them to discuss the study at this time will be offered Written informed consent will be obtained on the day of surgery prior to surgery Patients must not also require coronary artery surgery or be taking or receiving drugs that alter platelet function including aspirin within the past 2 weeks or any of the modern a ADP receptor antagonists such as Plavix As per current patient care guidelines at Strong Memorial Hospital patients undergoing first-time single valve non-coronary artery surgical procedures will be randomized to receive either epsilon aminocaproic acid EACA or aprotonin intravenously It is anticipated that 1-3 patients will be initially enrolled as pilot subjects to get the study going smoothly and that 1-3 patients may not be completed or that their testing andor data may be inadequate Therefore although the analysis will only use 40 subjects the protocol seeks permission to enroll a maximum of 24 subjects per group for a total of 48 patients
The tests to be performed are
1 the PFA-100 a platelet related hemostasis test which is a high shear system test of platelet function
2 the von Willebrand antigen test an immunoassay
3 factor VIII coagulant activity test
4 Ristocetin cofactor activity test
5 thromboelastography TEG a point-of-care test of hemostatic function which includes a measure of platelet function
Reference ranges coefficient of variation SDs for the tests are as follows
vWF-Ag 50 - 160 normal activity 2 - 5 5
FVIII 50 - 200 of normal 4 - 7 5
Ristocetin cofactor 60-200 of normal 15 10
PFA100 closure time epinephrine 181 seconds and ADP 112 seconds 12 20 secs
Total blood volume required from each patient for the purposes of doing the research related tests will be approximately 30 mls 1 fluid ounces or 2 tablespoons 10 mls will be drawn from each patients arterial line which is routinely placed for cardiac anesthesia surgery care at the following time points in their care
1 prior to induction of anesthesia
2 5 minutes after the loading dose of either EACA or aprotonin has been administered and prior to the administration of any heparin
3 15 minutes after the administration of protamine following termination of cardiopulmonary bypass
Thus no additional needle puncture will be necessary related to the study Each blood sample of 10 ml will be divided into one blue-top citrated tube 3 ml and kept on ice one blue-top citrated tube 3 ml and kept at room temperature and the remainder will be used to perform the TEG
IV Data Analysis and Monitoring
Statistical analysis will be performed using either a 2-sample t-test or the Mann-Whitney Test as appropriate to compare the two patient groups at each of the three time points A p-value of less than 005 will be considered significant All tests will be two-sided
With a proposed sample size of N 20 for each of the two groups the study will have at least 80 power to yield a statistically significant result
V Data Storage and Confidentiality
Data will be produced within the SMH hematology lab and then stored both on paper and on the computer in the Department of Anesthesiology and backed up on the network drive
The principal investigator will maintain the information in a password protected file on the computer in his their private office
The tests to be performed are
1 the PFA-100 a platelet related hemostasis test which is a high shear system test of platelet function
2 the von Willebrand antigen test an immunoassay
3 factor VIII coagulant activity test
4 Ristocetin cofactor activity test
5 thromboelastography TEG a point-of-care test of hemostatic function which includes a measure of platelet function
Reference ranges coefficient of variation SDs for the tests are as follows
vWF-Ag 50 - 160 normal activity 2 - 5 5
FVIII 50 - 200 of normal 4 - 7 5
Ristocetin cofactor 60-200 of normal 15 10
PFA100 closure time epinephrine 181 seconds and ADP 112 seconds 12 20 secs
Total blood volume required from each patient for the purposes of doing the research related tests will be approximately 30 mls 1 fluid ounces or 2 tablespoons 10 mls will be drawn from each patients arterial line which is routinely placed for cardiac anesthesia surgery care at the following time points in their care
1 prior to induction of anesthesia
2 5 minutes after the loading dose of either EACA or aprotonin has been administered and prior to the administration of any heparin
3 15 minutes after the administration of protamine following termination of cardiopulmonary bypass
Thus no additional needle puncture will be necessary related to the study Each blood sample of 10 ml will be divided into one blue-top citrated tube 3 ml and kept on ice one blue-top citrated tube 3 ml and kept at room temperature and the remainder will be used to perform the TEG
IV Data Analysis and Monitoring
Statistical analysis will be performed using either a 2-sample t-test or the Mann-Whitney Test as appropriate to compare the two patient groups at each of the three time points A p-value of less than 005 will be considered significant All tests will be two-sided
With a proposed sample size of N 20 for each of the two groups the study will have at least 80 power to yield a statistically significant result
V Data Storage and Confidentiality
Data will be produced within the SMH hematology lab and then stored both on paper and on the computer in the Department of Anesthesiology and backed up on the network drive
The principal investigator will maintain the information in a password protected file on the computer in his their private office
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None