The Effect of Serum LDL Lowering on Aspirin Resistance

February 19, 2013 updated by: Ziv Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Safed, Israel, 13110
        • Internal Medicine Department A ,Ziv Goverment Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ziv Hospital

Investigators

  • Principal Investigator: Osamah Hussein, MD, Internal Medicine Department A, Ziv Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Study Completion (Actual)

January 1, 2007

Study Registration Dates

First Submitted

April 25, 2007

First Submitted That Met QC Criteria

April 25, 2007

First Posted (Estimate)

April 27, 2007

Study Record Updates

Last Update Posted (Estimate)

February 20, 2013

Last Update Submitted That Met QC Criteria

February 19, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP 5-173 S

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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