HypercholesterolemiaPhase 4ROSEZENCT02772640
Effectiveness of Treatment of Hypercholesterolemia With Rosuvastatin and Ezetimibe
A Phase 4 study testing Rosuvastatin and Ezetimibe morning or evening administration in people with Hypercholesterolemia, run by Collegium Medicum w Bydgoszczy at 1 site in Poland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- Rosuvastatin and Ezetimibe morning or evening administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 1 sitePoland
- Study dates
- Mar 2016to May 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hypercholesterolemia
- Ineffectiveness of statin monotherapy in the treatment of hypercholesterolemia after at least 6 weeks
Who cannot join
- Active liver disease
- Unexplained persistent increase in serum transaminase levels, including more than 3 times the upper limit of normal activity of one of them
- Severe renal impairment (creatinine clearance <30 ml / min)
- Myopathy
- Concomitant treatment with cyclosporine, gemfibrozil
- Pregnancy
Show all 10Show fewer
- Lactation
- Women of childbearing age not using effective methods of contraception
- Symptoms of muscle damage after using statins or fibrates in the past.
- The activity of creatine kinase> 5 times the upper limit of normal
Trial locations and contacts
1 site in 1 country.
Poland1 site
Cardiology Department, Dr. A. Jurasz University Hospital
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094
About this study
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
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.
Read the 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.
- Conditions
- Hypercholesterolemia
- Being tested
- Rosuvastatin and Ezetimibe morning or evening administration
- Keywords
- Hypercholesterolemia, Rosuvastatin, Statin, Ezetimibe, Compliance, Cholesterol, Secondary prevention, Coronary artery disease, Cholesterol absorption inhibitor
- Medical subject headings
- Hypercholesterolemia, Patient Compliance, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosuvastatin and Ezetimibe morning or evening administrationDrug
Also called Rosuvastatin, Ezetimibe
Timing of the drug administration:
morning -> evening evening -> morning
| Study group | Role | What they receive |
|---|---|---|
| Arm I: R+E morning->evening | Active comparator | 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). Receives: Drug: Rosuvastatin and Ezetimibe morning or evening administration |
| ARM II: R+E evening->morning | Active comparator | 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). Receives: Drug: Rosuvastatin and Ezetimibe morning or evening administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total cholesterol and LDL-Cholesterol
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
Measured: 6 and 12 weeks
Secondary outcomes (13)
Change in HDL-Cholesterol
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
Measured: 6 and 12 weeks
Change in triglycerides
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
Measured: 6 and 12 weeks
Change in apolipoproteins ApoB, APO AI
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
Measured: 6 and 12 weeks
Change in non - HDL-Cholesterol
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
Measured: 6 and 12 weeks
Change in sd-LDL-Cholesterol
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
Measured: 6 and 12 weeks
Change in lipoprotein (a)
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
Measured: 6 and 12 weeks
Assessment of change of glucose concentration
Assessment of glucose at baseline and at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Assessment of HbA1c
Assessment of HbA1c at baseline and at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Assessment of hsCRP
Assessment hsCRP at baseline and at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Assessment of ALT
Assessment ALT at baseline and at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Assessment of AST
Assessment AST at baseline and at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Assessment of CK
Assessment CK at baseline and at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Assessment of plasma fluorescence using stationary and time-resolved spectrofluorimetry
Assessment of plasma fluorescence using stationary and time-resolved spectrofluorimetry at baseline, at 6 and 12 weeks of treatment with study drug
Measured: Baseline, 6 and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2016 (estimated)
- Study startMar 2016
- Primary completionJan 2019
- Study completionMay 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Collegium Medicum w Bydgoszczy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jacek Kubica, Collegium Medicum w Bydgoszczy
- Investigators
- Jacek Kubica, MD, PhD, Principal investigator, Collegium Medicum w Bydgoszczy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02772640
- Sponsor's protocol ID
- AMI9
- Acronym
- ROSEZE
- Status last verified
- Jan 2021
- First submitted
- 28 Mar 2016
- Last updated
- 2 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Obonska K, Kasprzak M, Sikora J, Obonska E, Racki K, Gozdzikiewicz N, Krintus M, Kubica J. The impact of the time of drug administration on the effectiveness of combined treatment of hypercholesterolemia with Rosuvastatin and Ezetimibe (RosEze): study protocol for a randomized controlled trial. Trials. 2017 Jul 11;18(1):316. doi: 10.1186/s13063-017-2047-8.
PubMed 28697767
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02772640
- Acronym / sponsor ID
- ROSEZE / AMI9
- Conditions
- Hypercholesterolemia
- Keywords
- Hypercholesterolemia, Rosuvastatin, Statin, Ezetimibe, Compliance, Cholesterol, Secondary prevention, Coronary artery disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Collegium Medicum w BydgoszczyUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- May 2020 (actual)
- First posted
- 13 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I: R+E morning->evening | Active comparator | Drug: Rosuvastatin and Ezetimibe morning or evening administrationRosuvastatin 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). |
| ARM II: R+E evening->morning | Active comparator | Drug: Rosuvastatin and Ezetimibe morning or evening administrationRosuvastatin 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). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Hypercholesterolemia
- Ineffectiveness of statin monotherapy in the treatment of hypercholesterolemia after at least 6 weeks
Key exclusion criteria (10 listed)
- Active liver disease
- Unexplained persistent increase in serum transaminase levels, including more than 3 times the upper limit of normal activity of one of them
- Severe renal impairment (creatinine clearance <30 ml / min)
- Myopathy
- Concomitant treatment with cyclosporine, gemfibrozil
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rosuvastatin and Ezetimibe morning or evening administrationAlso: Rosuvastatin, EzetimibeTiming of the drug administration: morning -> evening evening -> morning | Drug | ARM II: R+E evening->morning, Arm I: R+E morning->evening |
Primary outcome
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
13 secondary outcomes
Change in HDL-Cholesterol
Time frame: 6 and 12 weeks
Change in triglycerides
Time frame: 6 and 12 weeks
Change in apolipoproteins ApoB, APO AI
Time frame: 6 and 12 weeks
Change in non - HDL-Cholesterol
Time frame: 6 and 12 weeks
Change in sd-LDL-Cholesterol
Time frame: 6 and 12 weeks
Change in lipoprotein (a)
Time frame: 6 and 12 weeks
Assessment of change of glucose concentration
Time frame: Baseline, 6 and 12 weeks
Assessment of HbA1c
Time frame: Baseline, 6 and 12 weeks
Assessment of hsCRP
Time frame: Baseline, 6 and 12 weeks
Assessment of ALT
Time frame: Baseline, 6 and 12 weeks
Assessment of AST
Time frame: Baseline, 6 and 12 weeks
Assessment of CK
Time frame: Baseline, 6 and 12 weeks
Assessment of plasma fluorescence using stationary and time-resolved spectrofluorimetry
Time frame: Baseline, 6 and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2021.
- Derived from this study: PubMed 28697767Obonska K, Kasprzak M, Sikora J, Obonska E, Racki K, Gozdzikiewicz N, Krintus M, Kubica J. The impact of the time of drug administration on the effectiveness of combined treatment of hypercholesterolemia with Rosuvastatin and Ezetimibe (RosEze): study protocol for a randomized controlled trial. Trials. 2017 Jul 11;18(1):316. doi: 10.1186/s13063-017-2047-8.
- Study resultsLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacek Kubica, MD, PhD principal investigator
Collegium Medicum w Bydgoszczy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rosuvastatin and Ezetimibe morning or evening administration in people with Hypercholesterolemia, run by Collegium Medicum w Bydgoszczy at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total cholesterol and LDL-Cholesterol (time frame: 6 and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02772640, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2021.