The Effect of Serum LDL Lowering on Aspirin Resistance
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| ClinicalTrials.gov Identifier: NCT00466154 |
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Recruitment Status :
Completed
First Posted : April 27, 2007
Last Update Posted : February 20, 2013
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Aspirin resistance is the persistent platelet activation, demonstrated by platelet function tests (1).
The hypothesis is that:LDL 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 methods:Forty hypercholesterolemic patients with aspirin resistance after 5 days of treatment with aspirin and high LDL and triglycerides<300 mg/dL, will be enrolled.
Ten healthy volunteers will be the control group.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Aspirin Resistance Hypercholesterolemia | Drug: Aspirin | Not Applicable |
The patients will be treated by aspirin loading dose of 500mg and then 100 mg/day 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 (ALT,AST,GGT,Alkaline 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 (ALT,AST,GGT,Alkaline 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 solution(1.4% citric acid, 2.5% sodium citrate, and 2% dextrose) at a ratio of 9:1 (v:v) for washed platelets (WP)preparation.WP will be prepared by centrifugation at 240g for 20 min. The platelet bellet will be washed twice in 5 mmol Hepes buffer, pH 7.4 (140 mmol NaCl, 2 mmol KCL, 1 mmol MgCl2, 5 mmol Hepes, 12 mmol NaHCO3 and 5.5 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 6.5 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 ug/ml (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 (cm/min).
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 hexane:isopropanolol (3:2, v:v). 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 Type : | Interventional (Clinical Trial) |
| Enrollment : | 40 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | The Effect of Serum LDL Lowering on Aspirin Resistance |
| Study Start Date : | July 2005 |
| Actual Study Completion Date : | January 2007 |
- Spearsman's correlation coefficients will be calculated to determine the relation between changes in lipid parameters and changes in LDL tendency to oxidation and platelet aggregation.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Hypercholesterolemic low-moderate risk patients without hypolipidemic drugs for at least one month.
- Age ≥18 years on stable AHA step 1 diet.
- For primary prevention, LDL > 130 mg/dL and for secondary prevention LDL>70 and <100mg/dL. .
- CPK, ALT and AST < 1.5 x upper limit of normal at baseline.
Exclusion Criteria:
- Women currently receiving cyclical hormones.
- Treatment with hypolipidemic drugs during the last month.
- Oral corticosteroids, NSAID, COX-1 inhibitors and other antiplatelet drugs.
- Women with childbearing potential unless on safe contraception.
- Psychiatric disease with defect in judgement.
- Severe renal or hepatic diease.
- Uncontrolled hypo- or hyperthyroidism.
- Contraindication for ezetimibe or statin treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00466154
| Israel | |
| Internal Medicine Department A ,Ziv Goverment Hospital | |
| Safed, Israel, 13110 | |
| Principal Investigator: | Osamah Hussein, MD | Internal Medicine Department A, Ziv Medical Center |
| ClinicalTrials.gov Identifier: | NCT00466154 |
| Other Study ID Numbers: |
HP 5-173 S |
| First Posted: | April 27, 2007 Key Record Dates |
| Last Update Posted: | February 20, 2013 |
| Last Verified: | February 2013 |
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Aspirin resistance Platelet activation Hypercholesterolemia |
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Hypercholesterolemia Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Aspirin Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics |