Clinical trial NCT02726555: The Efficacy and Safety of Combined Therapy With Red Yeast Rice and Low-dose Statin：Comparing With Standardized Statin
Official title: Comparison Between Combined Therapy With Red Yeast Rice and Low-dose Statin and Standardized Statin: a Single-center, Non-inferiority, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Dyslipidemia
Atherosclerosis
Keywords: Red yeast rice
Atorvastatin
Mild cardiovascular disease
Lead sponsor: Wenzhou Medical University
Sponsor class: OTHER
First posted: 2016-04-01
Enrollment: 240
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Double-dose statin regimen achieves merely 6% of decrease in low-density lipoprotein cholesterol (LDL-C) levels, whereas the risk of side effects increased largely. The investigators' previous pilot study (NCT01686451) has suggested that red yeast rice was of similar lipid-lowering efficacy while was associated with less fatigue than statins. The purpose of this study is to evaluate the efficacy and safety of combined therapy with red yeast rice and low-dose atorvastatin in persons with mild atherosclerotic cardiovascular disease and who qualified for statin therapy according to national guidelines.

Detailed description: Both Red Yeast Rice and Statins are cholesterol-lowering medications are often prescribed for secondary prevention of cardiovascular disease (CVD). The investigators' previous pilot study (NCT01686451) has suggested that red yeast rice was of similar lipid-lowering efficacy while was associated with less fatigue than statins. The aim of this study is to compare the efficacy and safety of combined therapy with red yeast rice at 1.2 g/day and atorvastatin at 10 mg/day with atorvastatin at 20 mg/day in persons with mild atherosclerotic cardiovascular disease and who qualified for statin therapy according to national guidelines.

This study will enroll individuals with established mild atherosclerotic cardiovascular disease and who do not currently take lipid-lowering medications. Participants will be randomly assigned to receive combined therapy with red yeast rice at 1.2 g/day and atorvastatin at 10 mg/day or atorvastatin at 20 mg/day for 24 weeks. Study visits will occur at screening, baseline, week 4, week 8, week 16, and week 24. Blood will be collected for laboratory testing, and standardized questionnaires will assess noncardiovascular endpoints. Pill count will be used to assess adherence of treatment. Medication side effects will be monitored and tests of alanine aminotransferase (ALT), aspartate aminotransaminase (AST) and creatine phosphate kinase (CPK) will be performed. Medication efficacy will be assessed and test of low-density lipoprotein cholesterol (LDL-C) will be performed.

Eligibility criteria: Inclusion Criteria:

1. Patients with established mild atherosclerotic cardiovascular disease, defined as coronary and/or carotid and/or peripheral artery lesions \<40% lumen diameter stenosis, diagnosed by coronary angiography and carotid and/or peripheral artery ultrasound respectively, together with LDL cholesterol level \> 70 mg/dL (1.80 mmol/L).
2. Female patients must be postmenopausal as defined by no menstruation for at least 12 months, or surgically sterilized for at least three months prior to beginning the study, or have a negative pregnancy test and agree to avoid pregnancy during the study and one month after the end of the study by using two reliable methods of contraception.
3. Patients must have been informed of all aspects of the study and signed an informed consent form before any study-related activities.
4. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

Patients who have met all the above inclusion criteria will be screened for the following exclusion criteria.

1. Patients who have been taken lipid-lowering medications including statins or red yeast rice products during the 4 weeks prior to the screening visit.
2. Documented history of myocardial infarction (MI), unstable angina leading to hospitalization, uncontrolled cardiac arrhythmia, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), carotid surgery or stenting, cerebrovascular accident, transient ischemic attack, endovascular procedure or surgical intervention for peripheral vascular disease.
3. Planned to undergo scheduled PCI, CABG, carotid or peripheral revascularization during the study.
4. History of New York Heart Association Class III or IV heart failure within the past 12 months.
5. Known history of hemorrhagic stroke.
6. Patients with uncontrolled hypertension at the screening visit. Patients on stable antihypertensive medication may be enrolled provided that the medications and dosage remain stable throughout the study.
7. Cardiovascular surgery or major operations within 6 months prior to screening visit.
8. Patients who are taking anticoagulants except aspirin at \< 325 mg/day.
9. Patients with liver dysfunction as indicated by a serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) level of \> 1.5-times of upper limit of normal (ULN) range, or clinical symptoms.
10. Patients with elevated creatine phosphokinase level (above Upper Limit of Normal range).
11. Patients with renal dysfunction as indicated by a serum creatinine level above ULN range, or clinical symptoms.
12. Patients with gastric or peptic ulcer within 3 months prior to screening visit.
13. Patients with medical history of hypothyroidism, pancreatitis, cholestasis, nephrotic syndrome, gall bladder disease, or primary biliary cirrhosis. Patients on thyroid replacement therapy at stable doses may be enrolled if clinically euthyroid.
14. Patients with clinically relevant illness within 4 weeks prior to screening visit that may interfere with the conduct of this study.
15. Patients with a history of alcohol or narcotic substance abuse within two years prior to screening visit.
16. Patients with hypersensitivity to lipid-lowering agents.
17. Patients who have taken another investigational drug within 4 weeks prior to screening visit.
18. Patients with uncontrolled metabolic or endocrine disease knowing to influence lipid values.
19. Patients who are known to be HIV positive.
20. Patients who have a history or presence of active malignancy (other than non-melanoma skin cancer) or clinically significant psychiatric, neurological, respiratory, hematological, or other conditions that in the opinion of investigators might interfere with or contraindicate participation of the patients in this study.

Primary outcomes:
measure: Mean percentage change from baseline at week 24 (or the last assessment) on serum low-density lipoprotein cholesterol (LDL-C) level
timeFrame: Measured at screening, baseline, week 4, week 8, week 16, and week 24
Secondary outcomes:
measure: Mean percentage change from baseline at week 24 (or the last assessment on serum total cholesterol (TC) level
timeFrame: Measured at screening, baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on serum high-density lipoprotein cholesterol (HDL-C) level
timeFrame: Measured at screening, baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on serum triglyceride (TG) level
timeFrame: Measured at screening, baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on serum non-HDL cholesterol level
timeFrame: Measured at screening, baseline, week 4, week 8, week 16, and week 24
measure: Percentage of Participants Who Experienced Statin-associated muscle symptoms (SAMs)
timeFrame: Measured at week 4, week 8, week 16, and week 24
Other outcomes:
measure: Mean percentage change from baseline at week 24 (or the last assessment) on serum fasting blood glucose level
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on serum glycosylated hemoglobin level
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Physical Activity Level
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on fatigue scores
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Memory problems score
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Attention/concentration problems score
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Calculation problems score
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Depression/hopelessness score
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Anxiety score
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Mean percentage change from baseline at week 24 (or the last assessment) on Sleep problems score
timeFrame: Measured at baseline, week 4, week 8, week 16, and week 24
measure: Safety will be assessed by the incidence of adverse events (AEs), discontinuation due to the AEs, clinically relevant changes on laboratory test results, vital signs, physical examinations, and 12-lead electrocardiograms (ECG).
timeFrame: Screening, Baseline, Week 4, Week 8, week 16, and week 24
Locations:
city: Wenzhou
country: China
facility: The Second Hispital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: The Second Hispital of Wenzhou Medical University
name: Kangting Ji, MD
role: PRINCIPAL_INVESTIGATOR
References: