Ignite Creation Date:
2024-05-05 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00466154
Status:
COMPLETED
Last Update Posted:
2013-02-20
First Post:
2007-04-25
Brief Title:
The Effect of Serum LDL Lowering on Aspirin Resistance
Sponsor:
Ziv Hospital
Organization:
Ziv Hospital
Study Overview
Official Title:
The Effect of Serum LDL Lowering on Aspirin Resistance
Status:
COMPLETED
Status Verified Date:
2013-02
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:
Aspirin resistance is the persistent platelet activation demonstrated by platelet function tests 1
The hypothesis is thatLDL lowering by statin in patients with aspirin resistance can improve the effect of aspirin due to the potential decreasing of cholesterol content in the platelet membranes
Patients and methodsForty hypercholesterolemic patients with aspirin resistance after 5 days of treatment with aspirin and high LDL and triglycerides300 mgdL will be enrolled
Ten healthy volunteers will be the control group
The hypothesis is thatLDL lowering by statin in patients with aspirin resistance can improve the effect of aspirin due to the potential decreasing of cholesterol content in the platelet membranes
Patients and methodsForty hypercholesterolemic patients with aspirin resistance after 5 days of treatment with aspirin and high LDL and triglycerides300 mgdL will be enrolled
Ten healthy volunteers will be the control group
Detailed Description:
The patients will be treated by aspirin loading dose of 500mg and then 100 mgday for other 4 days For patients that will be entrolled in the regular working hours platelet aggregation test and cholesterol content in platelet membranes will be done at baseline
Blood tests for lipids liver ALTASTGGTAlkaline phosphatase and bilirubin and renal function tests blood urea nitrogen and creatinine complete blood count general urine test and serum homocysteine will be done on the second day
On the fifth day optical platelet aggregation test cholesterol content in platelet membranes platelet function in the PFA-100 system and soluble p-selectin in the plasma will be done If the patient has aspirin resistance platelet aggregation 20 with epinephrine or 70 with ADP LDL will be lowered in the plasma of 20 patients by hypolipidemic drugs statin alone or combined with ezetimibe Other 20 patients will continue to be treated by aspirin alone
One month later blood tests for lipids liver ALTASTGGTAlkaline phosphatase and bilirubin and renal function tests blood urea nitrogen and creatinine complete blood count general urine test and serum homocysteine will be done for the second time and platelet activity will be tested again for all patients
Platelet separation
For platelet studies venous blood 30 ml will be collected through siliconized syringes into acid citrate dextrose solution14 citric acid 25 sodium citrate and 2 dextrose at a ratio of 91 vv for washed platelets WPpreparationWP will be prepared by centrifugation at 240g for 20 min The platelet bellet will be washed twice in 5 mmol Hepes buffer pH 74 140 mmol NaCl 2 mmol KCL 1 mmol MgCl2 5 mmol Hepes 12 mmol NaHCO3 and 55 mmol of glucose For the preparation of WP suspension 15 uL of acetic acid 1mmol will be added to 1 ml of platelet suspension throughout WP preparation in order to ensure acidic conditions which are required for platelet resuspension This procedure will reduce the medium pH to 65 and it does not influence the aggregation response of the WP
Platelet aggregation
Collagen Nycomed germany will be used as the aggregating agent at a concentration of 4 ugml this concentration can cause up to 60 aggregation amplitude in WP Platelet aggregation will be perfomed at 37ºC in aggregometer using hepes as a reference system Results will be expressed as the extent of maximal aggregation of maximal amplitude and also as the slope of the aggregation curve cmmin
Cholesterol content in platelet membranes
Platelets will be washed three times with Hepes buffer and then sonicated twice for 20 seconds at 80 watt Platelet lipids will be extracted with hexaneisopropanolol 32 vv The cholesterol content will be measured in the dried hexane phase by the method of Chiamori et al 12 Platelet protein will be determined using the method of Lowry 13
Blood tests for lipids liver ALTASTGGTAlkaline phosphatase and bilirubin and renal function tests blood urea nitrogen and creatinine complete blood count general urine test and serum homocysteine will be done on the second day
On the fifth day optical platelet aggregation test cholesterol content in platelet membranes platelet function in the PFA-100 system and soluble p-selectin in the plasma will be done If the patient has aspirin resistance platelet aggregation 20 with epinephrine or 70 with ADP LDL will be lowered in the plasma of 20 patients by hypolipidemic drugs statin alone or combined with ezetimibe Other 20 patients will continue to be treated by aspirin alone
One month later blood tests for lipids liver ALTASTGGTAlkaline phosphatase and bilirubin and renal function tests blood urea nitrogen and creatinine complete blood count general urine test and serum homocysteine will be done for the second time and platelet activity will be tested again for all patients
Platelet separation
For platelet studies venous blood 30 ml will be collected through siliconized syringes into acid citrate dextrose solution14 citric acid 25 sodium citrate and 2 dextrose at a ratio of 91 vv for washed platelets WPpreparationWP will be prepared by centrifugation at 240g for 20 min The platelet bellet will be washed twice in 5 mmol Hepes buffer pH 74 140 mmol NaCl 2 mmol KCL 1 mmol MgCl2 5 mmol Hepes 12 mmol NaHCO3 and 55 mmol of glucose For the preparation of WP suspension 15 uL of acetic acid 1mmol will be added to 1 ml of platelet suspension throughout WP preparation in order to ensure acidic conditions which are required for platelet resuspension This procedure will reduce the medium pH to 65 and it does not influence the aggregation response of the WP
Platelet aggregation
Collagen Nycomed germany will be used as the aggregating agent at a concentration of 4 ugml this concentration can cause up to 60 aggregation amplitude in WP Platelet aggregation will be perfomed at 37ºC in aggregometer using hepes as a reference system Results will be expressed as the extent of maximal aggregation of maximal amplitude and also as the slope of the aggregation curve cmmin
Cholesterol content in platelet membranes
Platelets will be washed three times with Hepes buffer and then sonicated twice for 20 seconds at 80 watt Platelet lipids will be extracted with hexaneisopropanolol 32 vv The cholesterol content will be measured in the dried hexane phase by the method of Chiamori et al 12 Platelet protein will be determined using the method of Lowry 13
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