Phase IV Study to Evaluate the Effects of Statin Monotherapy or Statin / Ezetimibe Combination Therapy on Hepatic Steatosis in Patients With Hyperlipidemia and Nonalcoholic Fatty Liver Disease

NCT03434613 | Completed Phase 4

• 1 other identifier: 4-2017-1168
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the therapeutic effect of ezetimibe on nonalcoholic fatty liver disease, the effect of rosuvastatin 5mg monotherapy and rosuvastatin 5mg / ezetimibe 10mg combination therapy n patients with hyperlipidemia and fatty liver will be compared and analyzed. This study included a total of 70 patients (35 per subgroup) for randomized controlled trials with prospective, open label, randomized, single-institution clinical trials. The drug will be maintained for a total of six months. The primary endpoint is the difference of liver fat change measured by MRI-PDFF in colocalized regions of interest within nine liver segments between two groups.

Conditions

Nonalcoholic Fatty Liver Disease; Dyslipidemias

Outcome Measures

Primary Outcomes (1)

• liver fat change measured by MRI-PDFF in colocalized regions of interest within each of nine liver segments

  MRI is used to measure the fat fraction in 9 liver segments, and this test has been reported to be more sensitive than the biopsy-based steatosis grade assessment in confirming liver fat changes in previous studies

  6 months

Secondary Outcomes (20)

• Liver fibrosis measured by MRE(magnetic resonance elastography)

  6 months

• Change in hepatic steatosis index - controlled attenuation parameter (CAP)

  6 months

• Change in hepatic fibrosis index - liver stiffness measurement (LSM) measured by transient liver elastography (Fibroscan®; Echosens, Paris, France)

  6 months

• Changes in body weight (kg) before and after the administration of rosuvastatin with/without ezetimibe

  6 months

• Changes in waist circumference (cm) before and after the administration of rosuvastatin with/without ezetimibe

  6 months

Study Arms (2)

Rosuvastatin monotherapy

ACTIVE COMPARATOR

Rosuvastatin 5mg 1T daily for 6 months

Drug: Rosuvastatin

Rosuvastatin + ezetimibe combination therapy

EXPERIMENTAL

Rosuvastatin 5mg / Ezetimibe 10mg combination 1T daily for 6 months

Drug: Rosuvastatin/ezetimibe combination

Interventions

Rosuvastatin DRUG

Rosuvastatin 5mg 1T daily for 6 months

Rosuvastatin monotherapy

Rosuvastatin/ezetimibe combination DRUG

Rosuvastatin 5mg / Ezetimibe 10mg combination 1T daily for 6 months

Rosuvastatin + ezetimibe combination therapy

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ages 19 and over, under 80 years of age
• Patients diagnosed with fatty liver by abdominal ultrasonography or liver fibroscan. (In case of patients who were diagnosed fatty liver by liver scan, we will conduct abdominal ultrasonography for screening purposes)
• In the Domestic Dyslipidemia Treatment Guideline, patients with hyperlipidemia A. LDL-C is more than 130mg / dL when there is less than 1 major risk factor B. LDL-C 100 mg / dL or more if there are two or more major risk factors C. High-risk patients with carotid stenosis\> 50%, abdominal aortic aneurysm, and diabetes mellitus had LDL-C\> 70 mg / dL
• D. The main risk factors are as follows:
• i. smoking ii. Hypertension - systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg or antihypertensive iii. Low HDL cholesterol (\<40 mg / dL) iv. Age - Male 45+, Female 55+ v. Family history of early onset coronary artery disease - Parents, siblings with a history of coronary artery disease in men under 55 and women under 65 vi. High HDL cholesterol (60 mg / dL) or more is regarded as a protective factor and one of the total risk factors is reduced
• Even if it does not meet the criteria for hyperlipidemia, it is possible to select the subject when there is evidence of atherosclerosis on the test (carotid ultrasonography etc)
• Those who already use statin as a treatment for hyperlipemia should participate after a washout period of 1-2 weeks.
• Controlled diabetic patients (HbA1c ≤9.0%), no change in type of oral or injectable hypoglycemic agents for the last 12 weeks
• Those who voluntarily agreed to participate in clinical trials after hearing the explanation of the clinical trial
• Those who understand the content of the clinical trial and are able to participate in the trial by the end of the clinical trial

You may not qualify if:

• Diabetic patients other than type 2 diabetes, including type 1 diabetes and gestational diabetes
• Those who have a previous history of medication with ezetimibe or discontinuation due to side effects after medication
• Patients who have had a history of discontinuation of statin therapy due to side effects after medication,
• Unregulated diabetic patients (those who have changed the type of oral or injectable hypoglycemic agent within 12 weeks prior to Visit 1 or who have HbA1c\> 9.0% at screening time (Visit 1)
• patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma, and patients with a history of ketonic acidosis (within 6 months)
• Those who use thiazolidinedione and SGLT2i drugs which can affect fatty liver as a diabetes treatment drug
• Patients who meet the criteria for alcoholism in fatty liver disease (210 g / week for men in the last two years, 140 g / week for women)
• Chronic liver disease (including hemochromatosis, liver cancer, autoimmune liver disease, Child-Pugh score\> 7points, platelet \<75,000mm2, prothrombin time\> 16s), viral hepatitis -A, B,
• People who take drugs that can cause fatty liver (amiodarone, methotrexate, tamoxifen, valproate, corticosteroids, etc.)
• Patients who are allergic or hypersensitive to the drug or its constituents
• Patients who were treated with oral or parenteral corticosteroids chronic (within consecutive 14 days) within 8 weeks before screening
• Patients with genetic problems such as galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose uptake disorder
• Patients with malnutrition, starvation, weakness (including severe infections, pre- and post-operative trauma patients), pituitary dysfunction or adrenal insufficiency
• Serum levels of alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase are increased over 5-fold elevation of the normal range upper limit \[ULN\] or 5-fold elevation of the serum total bilirubin level. )
• Currently taking medication for weight loss

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes center

Seoul, 03722, South Korea

Location

Related Publications (2)

• Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, Soaft L, Hooker J, Kono Y, Bhatt A, Hernandez L, Nguyen P, Noureddin M, Haufe W, Hooker C, Yin M, Ehman R, Lin GY, Valasek MA, Brenner DA, Richards L; San Diego Integrated NAFLD Research Consortium (SINC). Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology. 2015 Apr;61(4):1239-50. doi: 10.1002/hep.27647. Epub 2015 Feb 27.

  PMID: 25482832 BACKGROUND

• Cho Y, Rhee H, Kim YE, Lee M, Lee BW, Kang ES, Cha BS, Choi JY, Lee YH. Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study). BMC Med. 2022 Mar 21;20(1):93. doi: 10.1186/s12916-022-02288-2.

  PMID: 35307033 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Dyslipidemias

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will conduct to evaluate the efficacy of liver fat lowering and safety of rosuvastatin 5mg alone or in combination with rosuvastatin 5mg / ezetimibe 10mg for 6 months.

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: May 14, 2018
• Primary Completion: September 11, 2019
• Study Completion: September 11, 2019
• Last Updated: July 9, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)