Efficacy and Safety of Rosuvastatin and Rosuvastatin/Ezetimibe Combination in High-Risk Hyperlipidemia Patients: A 12-Week Randomized Trial
- Trial ID
- 2023-504914-31-00
- Protocol
- KCT10/2022-LEASH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** and **safety** of treatment with high-intensity **rosuvastatin** or a single-pill combination of rosuvastatin/ezetimibe. The focus is on achieving the low-density lipoprotein cholesterol (LDL-C) treatment goal in patients at high or very high risk of cardiovascular disease (CVD) after 12 weeks of treatment. This is clinically relevant as achieving LDL-C targets is crucial in reducing the risk of cardiovascular events in patients with hyperlipidaemia.
Secondary objectives include:
- Assessing the pace of lowering lipid parameters and the proportion of patients achieving lipid goals, with a focus on the LDL-C treatment goal after 4, 8, or 12 weeks of treatment with high-intensity rosuvastatin or the single-pill combination of rosuvastatin/ezetimibe in high and very high-risk CVD patients.
Participants
The clinical trial involves a total of **118 participants** diagnosed with **hyperlipidaemia**. The study population comprises both male and female subjects, aged between 18 and 69 years. Participants were selected based on their high or very high cardiovascular disease (CVD) risk, with elevated low-density lipoprotein cholesterol (LDL-C) levels. The trial specifically includes individuals who are treatment-naïve to all lipid-lowering therapies. Participants are required to be capable of understanding the trial information and have voluntarily signed informed consent. The study excludes any vulnerable populations and focuses on individuals who can adhere to the trial protocol without any pathological clinical states or life-threatening illnesses that could affect compliance or survival. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of high-intensity **rosuvastatin** or a single-pill combination of **rosuvastatin/ezetimibe** in patients with **hyperlipidaemia** who are at high or very high cardiovascular disease (CVD) risk. This is a randomized, double-blind, controlled trial with an estimated duration of 12 weeks. The trial will include multiple study visits to monitor the progress and safety of the participants. The inclusion visit, also known as the screening visit, will assess the eligibility of participants based on specific criteria, including elevated LDL-C levels and age between 18 and 70 years. Participants must be treatment-naïve to lipid-lowering therapies and capable of adhering to the trial protocol.
Following the screening, participants will be randomized into two arms: one receiving high-intensity rosuvastatin and the other receiving the combination therapy. The primary endpoint is the proportion of patients achieving the LDL-C treatment goal after 12 weeks. Secondary endpoints include the proportion of patients achieving LDL-C reduction and target values at 4, 8, and 12 weeks, as well as changes in total cholesterol, non-HDL-C, HDL-C, and triglycerides. Study visits will occur at baseline, 4 weeks, 8 weeks, and 12 weeks, with each visit serving to assess the efficacy and safety of the treatment, as well as participant compliance.
The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including non-compliance with the trial protocol or the occurrence of adverse events that may compromise participant safety. The trial is set to begin recruitment in June 2024, with an estimated end date in April 2025. Participants will be monitored closely throughout the trial to ensure adherence to the protocol and to evaluate the therapeutic outcomes of the interventions.
Treatment
The clinical trial involves the administration of several **experimental medications** in the form of film-coated tablets, each containing **rosuvastatin** as the active ingredient. The first medication, Sorvasta 10 mg, is administered orally with a maximum daily dose of 10 mg. The treatment period for this medication is up to 8 weeks, with a total maximum dose of 560 mg. Compliance with the dosing schedule is monitored throughout the trial.
Sorvasta 20 mg is another experimental medication used in the trial. It is also a film-coated tablet containing **rosuvastatin** and is administered orally. The maximum daily dose for this formulation is 20 mg, with a total maximum dose of 1680 mg over a treatment period of up to 12 weeks. Participant adherence to the dosing regimen is closely monitored.
The trial also includes Sorvasta 40 mg, a film-coated tablet containing **rosuvastatin**. This medication is administered orally with a maximum daily dose of 40 mg. The treatment period for Sorvasta 40 mg is up to 8 weeks, with a total maximum dose of 2240 mg. Compliance with the prescribed dosing schedule is ensured through regular monitoring.
Additionally, the trial utilizes Sorvitimb 20 mg/10 mg, a combination film-coated tablet containing **ezetimibe** and **rosuvastatin**. This medication is administered orally with a maximum daily dose of 30 mg. The treatment period extends up to 12 weeks, with a total maximum dose of 2520 mg. Participant adherence to the dosing schedule is monitored throughout the study.
Sorvitimb 40 mg/10 mg is another combination film-coated tablet used in the trial, containing **ezetimibe** and **rosuvastatin**. It is administered orally with a maximum daily dose of 50 mg. The treatment period for this medication is up to 4 weeks, with a total maximum dose of 1400 mg. Compliance with the dosing regimen is closely monitored to ensure participant adherence.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. The focus of the trial is on the efficacy and safety of the experimental medications in achieving low-density lipoprotein cholesterol (LDL-C) treatment goals in patients at high or very high cardiovascular disease risk.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients at high or very high cardiovascular disease (CVD) risk. The primary endpoint is the proportion of patients achieving the LDL-C treatment goal after 12 weeks of treatment. This goal is defined as a reduction of LDL-C by at least 50% from baseline and achieving specific LDL-C levels: less than 1.4 mmol/L (55 mg/dL) for patients at very high CVD risk and less than 1.8 mmol/L (70 mg/dL) for patients at high CVD risk.
Secondary endpoints include the proportion of patients achieving the LDL-C treatment goal after 4 and 8 weeks, the proportion achieving a reduction of at least 50% in LDL-C from baseline at various time points, and the proportion achieving target non-HDL-C levels. Additionally, mean absolute and relative changes in total cholesterol (TC), LDL-C, non-HDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) will be measured. Compliance with the treatment regimen will also be assessed, with compliance defined as administering at least 80% of prescribed doses. Efficacy assessments will be conducted at baseline and at weeks 4, 8, and 12, corresponding to Visits 3, 4, and 5, respectively.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients at high or very high CVD risk# with elevated LDL-C levels: • LDL-C ≥1.8 mmol/L (70 mg/dL) if at high CVD risk OR • LDL-C ≥1.4 mmol/L (55 mg/dL) if at very high CVD risk _______________________ # Apparently healthy patients at high or very high CVD risk (according to SCORE2) OR patients with type II DM at high or very high CVD risk (if without previous ASCVD, CVD risk is assessed according to SCORE2-Diabetes) OR patients with ASCVD.
- Patients that are treatment-naїve* to all lipid-lowering therapy**. ________________________ *Patients who never received any lipid-lowering therapy** OR were not receiving any lipid-lowering therapy for at least 4 weeks before Visit 1. **Lipid-lowering therapy: therapy with statins, ezetimibe, fibrates, bile acid sequestrants, bempedoic acid, nicotinic acid and derivatives, PCSK9 inhibitors, any other study lipid-lowering drug or intake of Red Yeast Rice (RYR) containing supplements.
- Female or male patients aged ≥18$ and <70 years. ________________________ $Patients in the category of apparently healthy patients and patients with type II DM without ASCVD, must be ≥40 years old.
- Patients who have been provided with information about the trial, are capable of understanding the information (according to investigator’s judgement) and have voluntarily signed informed consent.
- Patients who have signed the consent for collection, analysis and processing of personal data, that will be collected during this clinical trial for the purpose of statistical analysis and final report of this clinical trial.
- Patients with the ability to adhere to and are compliant with the trial protocol according to investigator’s judgement (e.g. without pathological clinical states and any other life-threatening illness that could affect patient’s compliance or have any impact on patient’s survival rate based on the investigator’s judgement).
Exclusion Criteria
- Patients with known or suspected statin intolerance (according to patient’s medical history and investigator’s judgement), hypersensitivity or history of adverse reactions to the active substances rosuvastatin (or any other HMG-CoA reductase inhibitors) or ezetimibe (or any other lipid-lowering compounds that selectively inhibit the intestinal absorption of cholesterol) or to any of the excipients (e.g. rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption).
- Pregnancy, lactation and women of childbearing potential not using appropriate contraceptive measures (according to the Recommendations related to contraception and pregnancy testing in clinical trials).
- Patients currently participating in another clinical trial.
- Any acute disease (e.g. severe respiratory failure, severe infection, exacerbation or uncontrolled phase of a chronic disease, major trauma, surgery, COVID-19 or post-COVID-19/long COVID-19 syndromes diagnosed, etc.) within 30 days prior to screening visit.
- Any of the following laboratory findings: • moderate or severe renal impairment – eGFR (estimated glomerular filtration rate) <60 mL/min, • suspected or documented moderate or severe liver dysfunction, • active liver disease, including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation (AST or ALT) exceeding 3x the upper limit of normal (ULN), • significantly elevated levels of creatine kinase at the baseline (> 5xULN).
- Patients with diagnosed or suspected familial hypercholesterolaemia (FH).
- Patients with Chronic Kidney Disease (CKD).
- Patients with type II DM with diagnosed or suspected severe target organ damage (TOD).
- Patients with type II DM at moderate or low CVD risk (according to SCORE2-Diabetes algorithm).
- Patients of Asian ancestry.
- Diagnosed or suspected secondary dyslipidaemia/ hypercholesterolaemia (e.g. due to hypothyroidism).
- Patients with previously diagnosed specific type of genetic polymorphism that can lead to increased rosuvastatin exposure.
- Patients with diagnosed or suspected myopathy based on muscle symptoms and investigator’s judgement, a history of (statin-induced) myopathy, rhabdomyolysis or pre-disposing factors for myopathy/ rhabdomyolysis or patients with personal or family history of hereditary muscular disorders.
- Concomitant therapy with contraindicated active ingredients, such as drug combination of sofosbuvir/velpatasvir/voxilaprevir, cyclosporine, systemic formulation of fusidic acid within last 7 days and other medicinal products which may substantially increase or decrease rosuvastatin or ezetimibe plasma concentrations.
- Patients who have received LDL-C plasmapheresis treatment within 2 months prior to the screening visit (Visit 1), or have plans to receive it during the study.
- Surgical procedures planned to occur during trial (patients may be rescreened following completion of and recovery from the surgical procedure).
- Apparently healthy patients*, aged <40 years and with SBP ≥180 mmHg. _______________________ *Patients without established ASCVD and/or diabetes mellitus and/or CKD and/or familial hypercholesterolaemia, aged ≥ 40 years and with SBP < 180 mm Hg.
- Patients with type II DM without ASCVD, <40 years old.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Croatia | Not Recruiting | 03 Jun 2024 | 40 |
 Germany | Not Recruiting | 03 Jun 2024 | 10 |
 Hungary | Not Recruiting | 03 Jun 2024 | 40 |
 Poland | Not Recruiting | 03 Jun 2024 | 65 |
 Slovenia | Not Recruiting | 03 Jun 2024 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sorvasta 20 mg filmsko obložene tablete | Test | FILMSKO OBLOŽENE TABLETE | ORAL | 20 | 12 | PRD5425357 |
Sorvitimb 20 mg/10 mg filmsko obložene tablete | Test | FILMSKO OBLOŽENE TABLETE | ORAL | 30 | 12 | PRD7026766 |
Sorvasta 10 mg filmsko obložene tablete | Test | FILMSKO OBLOŽENE TABLETE | ORAL | 10 | 8 | PRD5425353 |
Sorvasta 40 mg filmsko obložene tablete | Test | FILMSKO OBLOŽENE TABLETE | ORAL | 40 | 8 | PRD5425361 |
Sorvitimb 40 mg/10 mg filmsko obložene tablete | Test | FILMSKO OBLOŽENE TABLETE | ORAL | 50 | 4 | PRD7026777 |