search
Back to results

Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation

Primary Purpose

Hypercholesterolemia

Status
Completed
Phase
Phase 4
Locations
Israel
Study Type
Interventional
Intervention
Simvastatin
Ezetimibe
Sponsored by
Ziv Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Hypercholesterolemic patients on stable simvastatin dose for at least one month.
  2. Age ≥18 years on stable AHA step 1 diet.
  3. Patients without CHD or with one risk factors ; LDL > 130 mg/dL and for Patients with CHD or CHD risk equivalent(clinical manifestations of non-coronary forms of atherosclerotic disease) or with 2 risk f actors (cigarette smoking, hypertension (BP ≥140/90 mm Hg or on antihypertensive medication), low HDL cholesterol (<40 mg/dL), family history of premature CHD;LDL>100 mg/dL
  4. Patients 'on at least simvastatin treatment of 20 mg per day.
  5. CPK, ALT and AST < 1.5 X upper limit of normal at baseline.

Exclusion Criteria:

  1. Women currently receiving cyclical hormones.
  2. Treatment with psyllium, other fiber based laxatives, phytosterol margarines, or other OTCs that affect serum lipids, unless treated with a stable regimen for > 6 weeks and the patient agrees to continue this regimen for the duration of the trial.
  3. Oral corticosteroids unless used as replacement therapy for pituitary/adrenal disease and a stable regimen for at least 6 weeks.
  4. Lipid lowering agents including fish oils and QUESTRAN taken within 6 weeks.
  5. Active coronary heart disease: unstable angina, acute myocardial infarction, CABG or PTCA within the last 3 months.
  6. Women with childbearing potential unless on safe contraception.
  7. Psychiatric disease with defect in judgement.
  8. Severe renal or hepatic disease.
  9. Uncontrolled hypo- or hyperthyroidism.
  10. Contraindication for ezetimibe or simvastatin treatment. The patients will continue on their treatment with simvastatin for 6 weeks, and then the patients will be treated by the same dose of simvastatin combined with ezetimibe 10 mg/day for other 6 weeks.

Sites / Locations

  • Internal Medicine Department A ,Ziv Goverment Hospital

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
April 25, 2007
Last Updated
February 19, 2013
Sponsor
Ziv Hospital
Collaborators
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT00466401
Brief Title
Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation
Official Title
Phase 4 Study on Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation In Hypercholesterolemic Patients on Simvastatin
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Ziv Hospital
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

5. Study Description

Brief Summary
The aim of our study is to Estimate the reduction of LDL by ezetimibe in hypercholesterolemic patients on simvastatin.Investigate the effect of LDL lowering by ezetimibe on platelet activity and LDL tendency to peroxidation in hypercholesterolemic patients on simvastatin therapy The hypothesis is that: LDL lowering by ezetimibe on-top of simvastatin in patients on fixed dose of simvastatin can reduce platelet aggregation, due to the potential decreasing of cholesterol content in the platelet membranes. LDL lowering by ezetimibe can lower LDL tendency to peroxidation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Type
Drug
Intervention Name(s)
Ezetimibe

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Hypercholesterolemic patients on stable simvastatin dose for at least one month. Age ≥18 years on stable AHA step 1 diet. Patients without CHD or with one risk factors ; LDL > 130 mg/dL and for Patients with CHD or CHD risk equivalent(clinical manifestations of non-coronary forms of atherosclerotic disease) or with 2 risk f actors (cigarette smoking, hypertension (BP ≥140/90 mm Hg or on antihypertensive medication), low HDL cholesterol (<40 mg/dL), family history of premature CHD;LDL>100 mg/dL Patients 'on at least simvastatin treatment of 20 mg per day. CPK, ALT and AST < 1.5 X upper limit of normal at baseline. Exclusion Criteria: Women currently receiving cyclical hormones. Treatment with psyllium, other fiber based laxatives, phytosterol margarines, or other OTCs that affect serum lipids, unless treated with a stable regimen for > 6 weeks and the patient agrees to continue this regimen for the duration of the trial. Oral corticosteroids unless used as replacement therapy for pituitary/adrenal disease and a stable regimen for at least 6 weeks. Lipid lowering agents including fish oils and QUESTRAN taken within 6 weeks. Active coronary heart disease: unstable angina, acute myocardial infarction, CABG or PTCA within the last 3 months. Women with childbearing potential unless on safe contraception. Psychiatric disease with defect in judgement. Severe renal or hepatic disease. Uncontrolled hypo- or hyperthyroidism. Contraindication for ezetimibe or simvastatin treatment. The patients will continue on their treatment with simvastatin for 6 weeks, and then the patients will be treated by the same dose of simvastatin combined with ezetimibe 10 mg/day for other 6 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Osamah Hussein, MD
Organizational Affiliation
Ziv Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Internal Medicine Department A ,Ziv Goverment Hospital
City
Safed
ZIP/Postal Code
13100
Country
Israel

12. IPD Sharing Statement

Citations:
PubMed Identifier
11558859
Citation
Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA, Knopp RH, Lipka LJ, Lebeaut AP, Yang B, Mellars LE, Cuffie-Jackson C, Veltri EP; Ezetimibe Study Group. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther. 2001 Aug;23(8):1209-30. doi: 10.1016/s0149-2918(01)80102-8. Erratum In: Clin Ther 2001 Sep;23(9):1601.
Results Reference
background
PubMed Identifier
12505224
Citation
Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, Suresh R, Sun S, Veltri EP. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002 Dec 18;40(12):2125-34. doi: 10.1016/s0735-1097(02)02610-4.
Results Reference
background
PubMed Identifier
11375333
Citation
van Heek M, Austin TM, Farley C, Cook JA, Tetzloff GG, Davis HR. Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters. Diabetes. 2001 Jun;50(6):1330-5. doi: 10.2337/diabetes.50.6.1330.
Results Reference
background
PubMed Identifier
14675576
Citation
Sager PT, Melani L, Lipka L, Strony J, Yang B, Suresh R, Veltri E; Ezetimibe Study Group. Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein. Am J Cardiol. 2003 Dec 15;92(12):1414-8. doi: 10.1016/j.amjcard.2003.08.048.
Results Reference
background
PubMed Identifier
11742881
Citation
Davis HR Jr, Compton DS, Hoos L, Tetzloff G. Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2032-8. doi: 10.1161/hq1201.100260.
Results Reference
background
PubMed Identifier
1861629
Citation
Lavy A, Brook GJ, Dankner G, Ben Amotz A, Aviram M. Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients. Metabolism. 1991 Aug;40(8):794-9. doi: 10.1016/0026-0495(91)90005-h.
Results Reference
background
PubMed Identifier
11476969
Citation
Hussein O, Frydman G, Frim H, Aviram M. Reduced susceptibility of low density lipoprotein to lipid peroxidation after cholestyramine treatment in heterozygous familial hypercholesterolemic children. Pathophysiology. 2001 Aug;8(1):21-28. doi: 10.1016/s0928-4680(01)00061-x.
Results Reference
background
PubMed Identifier
8380241
Citation
Surya II, Akkerman JW. The influence of lipoproteins on blood platelets. Am Heart J. 1993 Jan;125(1):272-5. doi: 10.1016/0002-8703(93)90096-r. No abstract available.
Results Reference
background
PubMed Identifier
2730708
Citation
Ardlie NG, Selley ML, Simons LA. Platelet activation by oxidatively modified low density lipoproteins. Atherosclerosis. 1989 Apr;76(2-3):117-24. doi: 10.1016/0021-9150(89)90094-4.
Results Reference
background
PubMed Identifier
9241100
Citation
Osamah H, Mira R, Sorina S, Shlomo K, Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets. Br J Clin Pharmacol. 1997 Jul;44(1):77-83. doi: 10.1046/j.1365-2125.1997.00625.x.
Results Reference
background
PubMed Identifier
6626183
Citation
Aviram M. Plasma lipoprotein separation by discontinuous density gradient ultracentrifugation in hyperlipoproteinemic patients. Biochem Med. 1983 Aug;30(1):111-8. doi: 10.1016/0006-2944(83)90013-3.
Results Reference
background
PubMed Identifier
12713767
Citation
Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, LeBeaut AP, Suresh R, Yang B, Veltri EP; Ezetimibe Study Group. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41. doi: 10.1016/s0195-668x(02)00807-2.
Results Reference
background

Learn more about this trial

Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation

We'll reach out to this number within 24 hrs