Effectiveness of Treatment of Hypercholesterolemia With Rosuvastatin and Ezetimibe
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the study is to demonstrate, whether the time of day of administration of the
      study drug (containing rosuvastatin and ezetimibe) has an impact on the effectiveness of
      lipid-lowering therapy.
    

Detailed description: 
      The current guidelines recommend statins as drugs of first choice in the treatment of
      hypercholesterolemia. If the target LDL cholesterol is not achieved, combination of a statin
      with a cholesterol absorption inhibitor -ezetimibe may be considered.

      According to meta-analyzes of studies assessing statins, each 1.0 mmol / L (~ 40 mg / dL)
      reduction in LDL-C corresponds to a 10% reduction in all-cause mortality and a 20% reduction
      in the number of deaths from coronary artery disease. Each 1 mmol / L (40 mg / dL) reduction
      in LDL-C also translates into a 23% and 17% reduction of the risk of major coronary events
      and stroke, respectively. Similar results concerning the efficacy and safety of
      lipid-lowering therapy using statins were obtained in meta-analyzes of studies on primary
      prevention. Statins are a heterogenous group of drugs with respect to their LDL-C reduction
      power. So far, the most potent statin is rosuvastatin. Despite intensive statin therapy
      provided, a large group of patients still does not reach therapeutic goals. Statin dose
      titration seems to be less effective compared with the combined therapy with statin and
      ezetimibe. The combination of statin with ezetimibe reduces the LDL-C by additional 15-20%.

      Tablets comprising both of these drugs (statin and ezetimibe) simplify the drug
      administration and increase the probability of drug compliance. This may increase the
      probability for achieving therapeutic goals in hypercholesterolemia treatment.

      Taking into account the metabolism of cholesterol and possible drug-drug interactions it is
      recommended to administer simvastatin in the evening. Rosuvastatin may be administer at any
      time of the day.

      The study is designed as an open-label, single-center, cross-over study evaluating the
      effectiveness of combined therapy with rosuvastatin and ezetimibe for hypercholesterolemia
      depending on timing of the day of administration of the study treatment. After enrollment the
      participants will be allocated into two arms, each receiving rosuvastatin and ezetimibe. The
      study drug (rosuvastatin with ezetimibe) will be given: 1) in the morning (8:00) for 6 weeks
      and then in the evening for the next 6 weeks; 2) in the evening (20:00) for the first 6 weeks
      and then in the morning for the following 6 weeks. The change in total cholesterol and
      LDL-cholesterol at 6 and 12 weeks of the tested therapy will be measured as the primary
      outcome of the study. Moreover, other parameters including: HDL-cholesterol, triglycerides,
      apolipoprotein B (ApoB), ApoAI, nonHDL-cholesterol, sd-LDL-cholesterol, lipoprotein (a),
      glucose, HBA1c, high sensitivity C reactive protein (hsCRP), ALT, aspartate aminotransferase
      (AST), creatine kinase (CK ) will be assessed as secondary outcomes.
    

Intervention name(s): Rosuvastatin and Ezetimibe morning or evening administration
Intervention type(s): Drug
Intervention description(s): Timing of the drug administration:
morning -> evening evening -> morning
Other intervention name(s): Rosuvastatin, Ezetimibe
Intervention MeSH terms: Rosuvastatin Calcium; Ezetimibe
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hypercholesterolemia; Rosuvastatin; Statin; Ezetimibe; Compliance; Cholesterol; Secondary prevention; Coronary artery disease; Cholesterol absorption inhibitor