ClinicalTrials.gov
ClinicalTrials.gov Menu

Effectiveness of Treatment of Hypercholesterolemia With Rosuvastatin and Ezetimibe (ROSEZE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02772640
Recruitment Status : Unknown
Verified May 2016 by Jacek Kubica, Collegium Medicum w Bydgoszczy.
Recruitment status was:  Recruiting
First Posted : May 13, 2016
Last Update Posted : May 25, 2016
Sponsor:
Information provided by (Responsible Party):
Jacek Kubica, Collegium Medicum w Bydgoszczy

Brief 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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Drug: Rosuvastatin and Ezetimibe morning or evening administration Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Impact of the Time of Drug Administration on the Effectiveness of Combined Treatment of Hypercholesterolemia With ROSuvastatin and EZEtimibe (ROSEZE) - A Single-center, Crossover, Open-label Study
Study Start Date : March 2016
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016


Arm Intervention/treatment
Active Comparator: Arm I: R+E morning->evening
Rosuvastatin and Ezetimibe morning or evening administration: Rosuvastatin (R) plus Ezetimibe (E) administration in the morning (8:00) for 6 weeks. After 6 weeks - intervention - change of the timing of study drug administration to the evening hours (20:00).
Drug: Rosuvastatin and Ezetimibe morning or evening administration

Timing of the drug administration:

morning -> evening evening -> morning

Other Name: Rosuvastatin, Ezetimibe

Active Comparator: ARM II: R+E evening->morning
Rosuvastatin and Ezetimibe evening or morning administration: Rosuvastatin (R) plus Ezetimibe (E) administration in the evening (20:00) for 6 weeks. After 6 weeks - intervention - change of the timing of study drug administration to the morning hours (8:00).
Drug: Rosuvastatin and Ezetimibe morning or evening administration

Timing of the drug administration:

morning -> evening evening -> morning

Other Name: Rosuvastatin, Ezetimibe




Primary Outcome Measures :
  1. Change in total cholesterol and LDL-Cholesterol [ Time Frame: 6 and 12 weeks ]
    Change in total cholesterol and LDL-Cholesterol at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration


Secondary Outcome Measures :
  1. Change in HDL-Cholesterol [ Time Frame: 6 and 12 weeks ]
    Change in HDL-Cholesterol at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration

  2. Change in triglycerides [ Time Frame: 6 and 12 weeks ]
    Change in triglycerides at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration

  3. Change in apolipoproteins ApoB, APO AI [ Time Frame: 6 and 12 weeks ]
    Change in apolipoproteins ApoB, APO AI at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration

  4. Change in non - HDL-Cholesterol [ Time Frame: 6 and 12 weeks ]
    Change in non - HDL-Cholesterol at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration

  5. Change in sd-LDL-Cholesterol [ Time Frame: 6 and 12 weeks ]
    Change in sd-LDL-Cholesterol at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration

  6. Change in lipoprotein (a) [ Time Frame: 6 and 12 weeks ]
    Change in lipoprotein (a) at 6 and 12 weeks of study drug treatment (combination of ezetimibe and rosuvastatin), depending on the time of day of study drug administration

  7. Assessment of change of glucose concentration [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment of glucose at baseline and at 6 and 12 weeks of treatment with study drug

  8. Assessment of HbA1c [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment of HbA1c at baseline and at 6 and 12 weeks of treatment with study drug

  9. Assessment of hsCRP [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment hsCRP at baseline and at 6 and 12 weeks of treatment with study drug

  10. Assessment of ALT [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment ALT at baseline and at 6 and 12 weeks of treatment with study drug

  11. Assessment of AST [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment AST at baseline and at 6 and 12 weeks of treatment with study drug

  12. Assessment of CK [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment CK at baseline and at 6 and 12 weeks of treatment with study drug

  13. Assessment of plasma fluorescence using stationary and time-resolved spectrofluorimetry [ Time Frame: Baseline, 6 and 12 weeks ]
    Assessment of plasma fluorescence using stationary and time-resolved spectrofluorimetry at baseline, at 6 and 12 weeks of treatment with study drug



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Hypercholesterolemia
  2. Ineffectiveness of statin monotherapy in the treatment of hypercholesterolemia after at least 6 weeks

Exclusion Criteria:

  1. Active liver disease
  2. Unexplained persistent increase in serum transaminase levels, including more than 3 times the upper limit of normal activity of one of them
  3. Severe renal impairment (creatinine clearance <30 ml / min)
  4. Myopathy
  5. Concomitant treatment with cyclosporine, gemfibrozil
  6. Pregnancy
  7. Lactation
  8. Women of childbearing age not using effective methods of contraception
  9. Symptoms of muscle damage after using statins or fibrates in the past.
  10. The activity of creatine kinase> 5 times the upper limit of normal

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02772640


Contacts
Contact: Karolina Obońska, MD, PhD +48525854023 kalaobonska@op.pl

Locations
Poland
Cardiology Department, Dr. A. Jurasz University Hospital Recruiting
Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-094
Contact: Karolina Obońska, MD, PhD    +48 52 5854023    kalaobonska@op.pl   
Sponsors and Collaborators
Collegium Medicum w Bydgoszczy
Investigators
Principal Investigator: Jacek Kubica, MD, PhD Collegium Medicum w Bydgoszczy

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jacek Kubica, Professor Jacek Kubica MD, PhD., Collegium Medicum w Bydgoszczy
ClinicalTrials.gov Identifier: NCT02772640     History of Changes
Other Study ID Numbers: AMI9
First Posted: May 13, 2016    Key Record Dates
Last Update Posted: May 25, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Jacek Kubica, Collegium Medicum w Bydgoszczy:
Hypercholesterolemia
Rosuvastatin
Statin
Ezetimibe
Compliance
Cholesterol
Secondary prevention
Coronary artery disease
Cholesterol absorption inhibitor

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Rosuvastatin Calcium
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors