Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation

NCT00466401 | Completed Phase 4

• 1 other identifier: HP-5-155-S
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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:

1. 1.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.
2. 2.LDL lowering by ezetimibe can lower LDL tendency to peroxidation.

Conditions

Hypercholesterolemia

Interventions

Simvastatin DRUG

Ezetimibe DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ziv Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Internal Medicine Department A ,Ziv Goverment Hospital

Safed, 13100, Israel

Location

Related Publications (12)

• 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.

  PMID: 11558859 BACKGROUND

• 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.

  PMID: 12505224 BACKGROUND

• 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.

  PMID: 11375333 BACKGROUND

• 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.

  PMID: 14675576 BACKGROUND

• 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.

  PMID: 11742881 BACKGROUND

• 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.

  PMID: 1861629 BACKGROUND

• 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.

  PMID: 11476969 BACKGROUND

• 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.

  PMID: 8380241 BACKGROUND

• 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.

  PMID: 2730708 BACKGROUND

• 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.

  PMID: 9241100 BACKGROUND

• 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.

  PMID: 6626183 BACKGROUND

• 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.

  PMID: 12713767 BACKGROUND

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Simvastatin; Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Osamah Hussein, MD

  Ziv Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: April 25, 2007
• First Posted: April 27, 2007
• Study Start: February 1, 2005
• Study Completion: August 1, 2007
• Last Updated: February 20, 2013

Record last verified: 2013-02

Locations

IL (1)