Clinical trial NCT00466401: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypercholesterolemia
Lead sponsor: Ziv Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2007-04-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Safed
country: Israel
facility: Internal Medicine Department A ,Ziv Goverment Hospital
Study officials:
affiliation: Ziv Hospital
name: Osamah Hussein, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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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.
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.
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.
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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.
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.