The Effect of Serum LDL Lowering on Aspirin Resistance

This study has been completed.
Sponsor:
Information provided by:
Ziv Hospital
ClinicalTrials.gov Identifier:
NCT00466154
First received: April 25, 2007
Last updated: February 19, 2013
Last verified: February 2013
  Purpose

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 Intervention
Aspirin Resistance
Hypercholesterolemia
Drug: Aspirin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Serum LDL Lowering on Aspirin Resistance

Resource links provided by NLM:


Further study details as provided by Ziv Hospital:

Primary Outcome Measures:
  • 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.

Estimated Enrollment: 40
Study Start Date: July 2005
Study Completion Date: January 2007
Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Hypercholesterolemic low-moderate risk patients without hypolipidemic drugs for at least one month.
  2. Age ≥18 years on stable AHA step 1 diet.
  3. For primary prevention, LDL > 130 mg/dL and for secondary prevention LDL>70 and <100mg/dL. .
  4. CPK, ALT and AST < 1.5 x upper limit of normal at baseline.

Exclusion Criteria:

  1. Women currently receiving cyclical hormones.
  2. Treatment with hypolipidemic drugs during the last month.
  3. Oral corticosteroids, NSAID, COX-1 inhibitors and other antiplatelet drugs.
  4. Women with childbearing potential unless on safe contraception.
  5. Psychiatric disease with defect in judgement.
  6. Severe renal or hepatic diease.
  7. Uncontrolled hypo- or hyperthyroidism.
  8. Contraindication for ezetimibe or statin treatment.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00466154

Locations
Israel
Internal Medicine Department A ,Ziv Goverment Hospital
Safed, Israel, 13110
Sponsors and Collaborators
Ziv Hospital
Investigators
Principal Investigator: Osamah Hussein, MD Internal Medicine Department A, Ziv Medical Center
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00466154     History of Changes
Other Study ID Numbers: HP 5-173 S
Study First Received: April 25, 2007
Last Updated: February 19, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Ziv Hospital:
Aspirin resistance
Platelet activation
Hypercholesterolemia

Additional relevant MeSH terms:
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
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 08, 2014