Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
6. februar 2018 oppdatert av: Antonio Hernandez Mijares, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
Coadministration of drugs is common in the pharmacologic treatment of dyslipidemia, with statins and ezetimibe generally constituting the medication of choice.
By acting at different levels, the combination of these drugs allows the therapeutic objective to be achieved.
However, it is not known how these drugs qualitatively affect the composition of lipoprotein subfractions, which differ in size and atherogenic potential.
The investigators set out to evaluate this effect as well as their effects on inflammatory, oxidative stress and endothelial function parameters.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
The study consisted of a randomised parallel trial and took place during a period of 2 months.
A total of 42 hyperlipidemic patients were randomly assigned to one of 2 groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
Studietype
Intervensjonell
Registrering (Faktiske)
42
Fase
- Ikke aktuelt
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- LDL cholesterol concentration of between 160-190 mg/dl in patients with less than 2 cardiovascular risk factors
- LDL concentration of between 130-160 mg/dl in patients that presented 2 or more cardiovascular risk factors.
Cardiovascular risk factors were defined as: age (≥ 45 years in men and ≥55 years in women), a smoking habit, hypertension (≥140/90 mmHg), diabetes mellitus, a high-density lipoprotein (HDL) cholesterol concentration of ≤ 40mg/dl, and a family history of cardiovascular disease.
Exclusion Criteria:
- Triglyceride concentration > 400 mg/dl
- Diabetes Mellitus
- Kidney, liver, or thyroid disease
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Simvastatin
Hyperlipidemic patients received simvastatin (40 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
|
simvastatin (40 mg/day) for 4 weeks
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
|
|
Eksperimentell: Ezetimibe
Hyperlipidemic patients received ezetimibe (10 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
|
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
ezetimibe (10 mg/day) for 4 weeks
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Total cholesterol concentration was measured by enzymatic assay
|
Baseline, 4 weeks and 8 weeks
|
|
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
|
Baseline, 4 weeks and 8 weeks
|
|
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
|
Baseline, 4 weeks and 8 weeks
|
|
Triglycerides Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Triglyceride concentration were measured by enzymatic assay
|
Baseline, 4 weeks and 8 weeks
|
|
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
|
Baseline, 4 weeks and 8 weeks
|
|
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
LDL subfractions were separated by high-resolution polyacrylamide gel tubes using the Lipoprint® system.
The LDL electrophoretic profile allows 2 patterns to be defined: pattern A or large and buoyant LDL, and pattern non-A or small and dense LDL.
|
Baseline, 4 weeks and 8 weeks
|
|
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Levels of apolipoprotein B were determined by inmunonephelometry
|
Baseline, 4 weeks and 8 weeks
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
|
Baseline, 4 weeks and 8 weeks
|
|
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Membrane Potential Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.
Leukocyte rolling was estimated as the number of leukocytes rolling over 100 μm2 of the endothelial monolayer during a 1-min period.
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.
Adhesion was evaluated by counting the number of polymorphonuclear cells that maintained stable contact with human umbilical vein endothelial cells (HUVEC) for 30 seconds.
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.The rolling velocity in the field of focus was determined by measuring the time required by 20 consecutive leukocytes to cover a distance of 100 μm.
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
Tidsramme: Baseline, 4 weeks and 8 weeks
|
E-selectin was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Antonio Hernández, MD, Phd, FISABIO - University Hospital Dr Peset
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Berneis K, Rizzo M, Berthold HK, Spinas GA, Krone W, Gouni-Berthold I. Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial. Eur Heart J. 2010 Jul;31(13):1633-9. doi: 10.1093/eurheartj/ehq181. Epub 2010 Jun 6.
- Florentin M, Liberopoulos EN, Moutzouri E, Rizos CV, Tselepis AD, Elisaf MS. The effect of simvastatin alone versus simvastatin plus ezetimibe on the concentration of small dense low-density lipoprotein cholesterol in subjects with primary hypercholesterolemia. Curr Med Res Opin. 2011 Mar;27(3):685-92. doi: 10.1185/03007995.2010.546394. Epub 2011 Jan 27.
- Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, Johnson-Levonas AO, Sapre A, Donahue SR; Ezetimibe Study Group. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758-73. doi: 10.1016/j.clinthera.2004.11.016.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. januar 2009
Primær fullføring (Faktiske)
1. desember 2011
Studiet fullført (Faktiske)
1. desember 2011
Datoer for studieregistrering
Først innsendt
25. november 2014
Først innsendt som oppfylte QC-kriteriene
26. november 2014
Først lagt ut (Anslag)
2. desember 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
8. mars 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
6. februar 2018
Sist bekreftet
1. februar 2018
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Metabolske sykdommer
- Lipidmetabolismeforstyrrelser
- Dyslipidemier
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antimetabolitter
- Antikolesteremiske midler
- Hypolipidemiske midler
- Lipidregulerende midler
- Hydroksymetylglutaryl-CoA-reduktasehemmere
- Simvastatin
- Ezetimibe
- Ezetimib, Simvastatin medikamentkombinasjon
Andre studie-ID-numre
- SIM-EZE-2009-01
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .