Background: Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux.Methods/design: The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study.Discussion: The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number: ClinicalTrials (NCT): NCT01031667.
Bibliographical noteFunding Information:
target lesions. Lipid profiles, to include total cholesterol, LDL, HDL, triglyceride, apolipoprotein A-1 and B, LDL particle size and HDL subfractions, and biomarkers associated with atherosclerosis, including high-sensitivity C-reactive protein (hsCRP), oxidized LDL, VCAM-1, von Willebrand factor (vWF) and lipoprotein (a) [Lp(a)], will be measured at enrollment, and at 1-and 9-month follow-up examinations. The trial algorithm is shown in Figure 1. This is an investigator-initiated clinical trial with grant support from Korea Otska Pharmaceutical Co. Ltd (Seoul, Korea). Other than providing financial support, the company is not involved in developing study protocols or study processes, including site selection, management, and data collection and analysis. The study is performed according to the principles of the Declaration of Helsinki and according to common guidelines for clinical trials (ICH-GCP). The authors are solely responsible for the design and editing of this paper and its final content. The trial protocol has been approved by the local institutional review boards of each patient-enrolling center, and has been registered at http://www.clinicaltrials.gov (NCT01031667). Patient information, blood samples, and IVUS, VH and coronary angiogram images will be coded with the identification number of this study; investigators are blinded to patient identifying information, which has been replaced with a coded number.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Pharmacology (medical)