Dyslipidemias
Conditions
Brief summary
Both XueZhiKang and Statins are cholesterol-lowering medications that are often prescribed for individuals with high cholesterol and who are at risk for cardiovascular disease (CVD). Several studies, including one randomized, double-blind, placebo-controlled clinical trial, have suggested that the use of statins is more frequently associated with fatigue. And XueZhiKang may be not. The purpose of this study is to compare the effect of these two medications on fatigue in persons who are at moderate to low CVD risk based on the risk estimation system in ESC(European Society of Cardiology)/ESA(European Atherosclerosis Society) guidelines (2011) for the management of dyslipidemias.
Detailed description
Individuals at risk for cardiovascular disease (CVD) are often prescribed statins, which are medications that reduce the amount of cholesterol in the blood. By lowering cholesterol levels, these individuals have a lower incidence of coronary artery disease, ischemic stroke, and peripheral arterial disease and so on. While statins are effective at lowering cholesterol levels, their effect on fatigue is obvious and has been suggested by several studies, including one randomized, double-blind, placebo-controlled clinical trial. And XueZhiKang may be not. The purpose of this study is to compare the effect of these two medications on fatigue in persons who are at moderate to low CVD risk based on the risk estimation system in ESC(European Society of Cardiology)/ESA(European Atherosclerosis Society) guidelines (2011) for the management of dyslipidemias. This study will enroll individuals who do not currently take cholesterol-lowering medications. Participants will be randomly assigned to receive 600mg of XueZhiKang twice a day, or 20mg of simvastatin daily for 4 weeks. Study visits will occur at baseline and Week 4. Blood will be collected for laboratory testing, and standardized psychological questionnaires will assess fatigue scores and physical activity levels at baseline and week 4. Pill count will be used to assess adherence of XueZhiKang and simvastatin treatment at week 4. At week 4, medication side effects will be monitored and tests of alanine aminotransferase (ALT), aspartate aminotransaminase (AST) and creatine phosphate kinase (CPK) will be performed. At week 4, medication efficacy will be assessed and test of low-density lipoprotein cholesterol (LDL-C) will be performed.
Interventions
DRUGXueZhiKang
Participants will receive 600mg of XueZhiKang twice a day for 4 weeks.
DRUGsimvastatin
Participants will receive 20mg of simvastatin daily for 4 weeks.
Sponsors
Wenzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. LDL cholesterol level between 115-190 mg/dL; 2. Able to fast prior to blood draw; 3. Able to comfortably read and write in Chinese; 4. Able and willing to refrain from donating whole blood during study participation; 5. Willing to abstain from consuming large amounts of grapefruit juice.
Exclusion criteria
1. Current use of lipid-lowering medications; 2. Documented cardiovascular disease (CVD) by invasive or non-invasive testing (such as coronary angiography, nuclear imaging, stress echocardiography, carotid plaque on ultrasound), previous myocardial infarction (MI), acute coronary syndrome (ACS), coronary revascularization \[percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG)\] and other arterial revascularization procedures, ischaemic stroke, peripheral arterial disease(PAD); 3. Patients with type 2 diabetes, patients with type 1 diabetes with target organ damage (such as microalbuminuria); 4. Patients with moderate to severe chronic kidney disease \[glomerular filtration rate (GFR) \< 60 mL/min/1.73㎡\]; 5. Markedly elevated single risk factors such as familial dyslipidaemias and severe hypertension; 6. A calculated SCORE ≥5% for 10 year risk of fatal CVD; 7. Cancer; 8. HIV infected; 9. Medical or psychiatric condition that prevents full study participation or follow-up (e.g., active psychosis); 10. Active liver disease or unexplained persistent elevated transaminase levels； 11. Major surgery or hospitalization in the 3 months prior to study entry; 12. Current use of cyclosporin, erythromycin, clarithromycin, nefazodone, or any azole antifungals, including fluconazole, itraconazole, ketoconazole, mibefradil, or protease inhibitors; 13. Female of childbearing potential; 14. Current participation in another clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison Between XueZhiKang and Simvastatin on Fatigue Scores | Measured at baseline and week 4 | At baseline and week 4, the fatigue score was assessed by a fatigue questionnaire named as Fatigue Assessment Scale (FAS) which used 10-item fatigue measure with the fatigue score ranged from 10-50. The higher score was meaning of higher level of fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Efficacy | Measured at baseline and week 4 | Treatment efficacy was estimated on the basis of triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), as well as LDL-C levels obtained at baseline and week 4. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Measured at baseline and week 4 | At baseline and week 4, we estimated physical activity level by short version of international physical activity questionnaire (IPAQ) with categorical score ranged from low to high. The higher score was meaning of lower physical activity level. |
| Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | Measured at baseline and week 4 | Fasting blood samples were collected at weeks 0 (randomization) and 4 (end of study) for clinical chemistry. |
| Comparison of Safety Laboratory Testing (Cr) Between Simvastatin- and Xuezhikang-group | Measured at baseline and week 4 | Fasting blood samples were collected at weeks 0 (randomization) and 4 (end of study) for clinical chemistry. |
| Treatment Adherence at Week 4 in Simvastatin- and Xuezhikang-group | Measured at baseline and week 4 | We counted the total number of pills that were dispensed to the participants at baseline and the total number of pills that were taken by participants at week 4. |
Countries
China
Participant flow
Recruitment details
From August 10, 2012, through September 15, 2013, 243 patients were screened and 60 patients who met the inclusion criteria were enrolled and randomly assigned to either simvastatin (33 patients) or xuezhikang (27 patients) at medical clinic.
Pre-assignment details
183 eligible patients were excluded with 160 patients declined to participate while 19 patients were currently using lipid-lowering medications, 3 patients were suffering from chronic kidney disease or active liver disease and 1 was of currently childbearing.
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Participants will receive 20mg of simvastatin daily for 4 weeks.
simvastatin : Participants will receive 20mg of simvastatin daily for 4 weeks. | 33 |
| XueZhiKang Participants will receive 600mg of XueZhiKang twice a day for 4 weeks.
XueZhiKang : Participants will receive 600mg of XueZhiKang twice a day for 4 weeks. | 27 |
| Total | 60 |
Baseline characteristics
| Characteristic | XueZhiKang | Simvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 33 Participants | 60 Participants |
| Age, Continuous | 47.04 years STANDARD_DEVIATION 5.83 | 46.18 years STANDARD_DEVIATION 7 | 46.57 years STANDARD_DEVIATION 6.46 |
| Alanine aminotransferase, Continuous | 30.33 U/L STANDARD_DEVIATION 13.3 | 28.58 U/L STANDARD_DEVIATION 10.55 | 29.37 U/L STANDARD_DEVIATION 11.79 |
| Arterial blood pressure, Continuous Diastolic blood pressure | 83.00 mmHg STANDARD_DEVIATION 8.82 | 84.18 mmHg STANDARD_DEVIATION 6.95 | 83.65 mmHg STANDARD_DEVIATION 7.8 |
| Arterial blood pressure, Continuous Systolic blood pressure | 147.89 mmHg STANDARD_DEVIATION 17.03 | 148.06 mmHg STANDARD_DEVIATION 18.51 | 147.98 mmHg STANDARD_DEVIATION 17.71 |
| Arterial hypertension, Categorical Arterial hypertension | 16 participants | 26 participants | 42 participants |
| Arterial hypertension, Categorical Not Arterial hypertension | 11 participants | 7 participants | 18 participants |
| Aspartate aminotransferase, Continuous | 25.63 U/L STANDARD_DEVIATION 7.53 | 24.12 U/L STANDARD_DEVIATION 7 | 24.80 U/L STANDARD_DEVIATION 7.22 |
| Creatine phosphate kinase, Continuous | 91.65 U/L STANDARD_DEVIATION 23.71 | 80.82 U/L STANDARD_DEVIATION 24.91 | 85.69 U/L STANDARD_DEVIATION 24.78 |
| Creatinine, Continuous | 75.59 μmol/L STANDARD_DEVIATION 17.2 | 72.57 μmol/L STANDARD_DEVIATION 14.44 | 73.93 μmol/L STANDARD_DEVIATION 15.68 |
| Current cigarette smoker, Categorical Current cigarette smoker | 2 participants | 3 participants | 5 participants |
| Current cigarette smoker, Categorical Not Current cigarette smoker | 25 participants | 30 participants | 55 participants |
| Fasting blood glucose, Continuous | 5.33 mmol/L STANDARD_DEVIATION 0.52 | 5.10 mmol/L STANDARD_DEVIATION 0.36 | 5.20 mmol/L STANDARD_DEVIATION 0.45 |
| Fatigue score, Continuous | 19.26 units on a scale STANDARD_DEVIATION 1.85 | 19.58 units on a scale STANDARD_DEVIATION 2.55 | 19.43 units on a scale STANDARD_DEVIATION 2.25 |
| High-density lipoprotein-cholesterol, Continuous | 1.23 mmol/L STANDARD_DEVIATION 0.25 | 1.27 mmol/L STANDARD_DEVIATION 0.25 | 1.26 mmol/L STANDARD_DEVIATION 0.25 |
| Low-density lipoprotein-cholesterol, Continuous | 3.74 mmol/L STANDARD_DEVIATION 0.55 | 3.72 mmol/L STANDARD_DEVIATION 0.48 | 3.73 mmol/L STANDARD_DEVIATION 0.5 |
| Physical activity level, Categorical High level | 12 participants | 9 participants | 21 participants |
| Physical activity level, Categorical Low level | 3 participants | 14 participants | 17 participants |
| Physical activity level, Categorical Moderate level | 12 participants | 10 participants | 22 participants |
| Region of Enrollment China | 27 participants | 33 participants | 60 participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28 Participants |
| Sex: Female, Male Male | 14 Participants | 18 Participants | 32 Participants |
| Total cholesterol, Continuous | 5.82 mmol/L STANDARD_DEVIATION 0.73 | 5.91 mmol/L STANDARD_DEVIATION 0.71 | 5.87 mmol/L STANDARD_DEVIATION 0.72 |
| Triglyceride, Continuous | 1.61 mmol/L STANDARD_DEVIATION 0.65 | 1.76 mmol/L STANDARD_DEVIATION 1 | 1.69 mmol/L STANDARD_DEVIATION 0.86 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 33 | 0 / 27 |
| serious Total, serious adverse events | 0 / 33 | 0 / 27 |
Outcome results
Primary
Comparison Between XueZhiKang and Simvastatin on Fatigue Scores
At baseline and week 4, the fatigue score was assessed by a fatigue questionnaire named as Fatigue Assessment Scale (FAS) which used 10-item fatigue measure with the fatigue score ranged from 10-50. The higher score was meaning of higher level of fatigue.
Time frame: Measured at baseline and week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin/Baseline | Comparison Between XueZhiKang and Simvastatin on Fatigue Scores | 19.58 units on a scale | Standard Deviation 2.55 |
| Simvastatin/Week 4 | Comparison Between XueZhiKang and Simvastatin on Fatigue Scores | 21.58 units on a scale | Standard Deviation 2.75 |
| XueZhiKang/Baseline | Comparison Between XueZhiKang and Simvastatin on Fatigue Scores | 19.26 units on a scale | Standard Deviation 1.85 |
| XueZhiKang/Week 4 | Comparison Between XueZhiKang and Simvastatin on Fatigue Scores | 19.33 units on a scale | Standard Deviation 1.9 |
Secondary
Treatment Efficacy
Treatment efficacy was estimated on the basis of triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), as well as LDL-C levels obtained at baseline and week 4.
Time frame: Measured at baseline and week 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simvastatin/Baseline | Treatment Efficacy | TG level at baseline and week 4 | 1.76 mmol/L | Standard Deviation 1 |
| Simvastatin/Baseline | Treatment Efficacy | TC level at baseline and week 4 | 5.91 mmol/L | Standard Deviation 0.71 |
| Simvastatin/Baseline | Treatment Efficacy | LDL level at baseline and week 4 | 3.72 mmol/L | Standard Deviation 0.48 |
| Simvastatin/Baseline | Treatment Efficacy | HDL level at baseline and week 4 | 1.27 mmol/L | Standard Deviation 0.25 |
| Simvastatin/Week 4 | Treatment Efficacy | TG level at baseline and week 4 | 1.54 mmol/L | Standard Deviation 1.01 |
| Simvastatin/Week 4 | Treatment Efficacy | LDL level at baseline and week 4 | 2.54 mmol/L | Standard Deviation 0.72 |
| Simvastatin/Week 4 | Treatment Efficacy | TC level at baseline and week 4 | 4.73 mmol/L | Standard Deviation 1.08 |
| Simvastatin/Week 4 | Treatment Efficacy | HDL level at baseline and week 4 | 1.32 mmol/L | Standard Deviation 0.36 |
| XueZhiKang/Baseline | Treatment Efficacy | TG level at baseline and week 4 | 1.61 mmol/L | Standard Deviation 0.65 |
| XueZhiKang/Baseline | Treatment Efficacy | LDL level at baseline and week 4 | 3.74 mmol/L | Standard Deviation 0.55 |
| XueZhiKang/Baseline | Treatment Efficacy | HDL level at baseline and week 4 | 1.23 mmol/L | Standard Deviation 0.25 |
| XueZhiKang/Baseline | Treatment Efficacy | TC level at baseline and week 4 | 5.82 mmol/L | Standard Deviation 0.73 |
| XueZhiKang/Week 4 | Treatment Efficacy | LDL level at baseline and week 4 | 2.45 mmol/L | Standard Deviation 0.71 |
| XueZhiKang/Week 4 | Treatment Efficacy | TG level at baseline and week 4 | 1.36 mmol/L | Standard Deviation 0.69 |
| XueZhiKang/Week 4 | Treatment Efficacy | TC level at baseline and week 4 | 4.72 mmol/L | Standard Deviation 1.16 |
| XueZhiKang/Week 4 | Treatment Efficacy | HDL level at baseline and week 4 | 1.37 mmol/L | Standard Deviation 0.44 |
Other Pre-specified
Comparison of Safety Laboratory Testing (Cr) Between Simvastatin- and Xuezhikang-group
Fasting blood samples were collected at weeks 0 (randomization) and 4 (end of study) for clinical chemistry.
Time frame: Measured at baseline and week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin/Baseline | Comparison of Safety Laboratory Testing (Cr) Between Simvastatin- and Xuezhikang-group | 72.57 mmol/L | Standard Deviation 14.44 |
| Simvastatin/Week 4 | Comparison of Safety Laboratory Testing (Cr) Between Simvastatin- and Xuezhikang-group | 71.95 mmol/L | Standard Deviation 14.34 |
| XueZhiKang/Baseline | Comparison of Safety Laboratory Testing (Cr) Between Simvastatin- and Xuezhikang-group | 75.59 mmol/L | Standard Deviation 17.2 |
| XueZhiKang/Week 4 | Comparison of Safety Laboratory Testing (Cr) Between Simvastatin- and Xuezhikang-group | 76.51 mmol/L | Standard Deviation 16.39 |
Other Pre-specified
Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups
Fasting blood samples were collected at weeks 0 (randomization) and 4 (end of study) for clinical chemistry.
Time frame: Measured at baseline and week 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simvastatin/Baseline | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | CPK level at baseline and week 4 | 80.82 U/L | Standard Deviation 24.91 |
| Simvastatin/Baseline | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | AST level at baseline and week 4 | 24.12 U/L | Standard Deviation 6.99 |
| Simvastatin/Baseline | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | ALT level at baseline and week 4 | 28.58 U/L | Standard Deviation 10.55 |
| Simvastatin/Week 4 | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | CPK level at baseline and week 4 | 82.76 U/L | Standard Deviation 33.8 |
| Simvastatin/Week 4 | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | ALT level at baseline and week 4 | 28.73 U/L | Standard Deviation 13.1 |
| Simvastatin/Week 4 | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | AST level at baseline and week 4 | 24.42 U/L | Standard Deviation 6.89 |
| XueZhiKang/Baseline | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | ALT level at baseline and week 4 | 30.33 U/L | Standard Deviation 13.3 |
| XueZhiKang/Baseline | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | CPK level at baseline and week 4 | 91.65 U/L | Standard Deviation 23.71 |
| XueZhiKang/Baseline | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | AST level at baseline and week 4 | 25.63 U/L | Standard Deviation 7.53 |
| XueZhiKang/Week 4 | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | AST level at baseline and week 4 | 25.85 U/L | Standard Deviation 7.24 |
| XueZhiKang/Week 4 | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | CPK level at baseline and week 4 | 90.92 U/L | Standard Deviation 24.36 |
| XueZhiKang/Week 4 | Comparison of Safety Laboratory Testings (ALT,AST,CPK) Between Simvastatin- and Xuezhikang-groups | ALT level at baseline and week 4 | 28.67 U/L | Standard Deviation 14.73 |
Other Pre-specified
Comparison of XueZhiKang With Simvastatin of Physical Activity Level
At baseline and week 4, we estimated physical activity level by short version of international physical activity questionnaire (IPAQ) with categorical score ranged from low to high. The higher score was meaning of lower physical activity level.
Time frame: Measured at baseline and week 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Simvastatin/Baseline | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Low level at baseline and week 4 | 14 participants |
| Simvastatin/Baseline | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | High level at baseline and week 4 | 9 participants |
| Simvastatin/Baseline | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Moderate level at baseline and week 4 | 10 participants |
| Simvastatin/Week 4 | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Low level at baseline and week 4 | 25 participants |
| Simvastatin/Week 4 | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | High level at baseline and week 4 | 0 participants |
| Simvastatin/Week 4 | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Moderate level at baseline and week 4 | 8 participants |
| XueZhiKang/Baseline | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Moderate level at baseline and week 4 | 12 participants |
| XueZhiKang/Baseline | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Low level at baseline and week 4 | 3 participants |
| XueZhiKang/Baseline | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | High level at baseline and week 4 | 12 participants |
| XueZhiKang/Week 4 | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Low level at baseline and week 4 | 3 participants |
| XueZhiKang/Week 4 | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | High level at baseline and week 4 | 9 participants |
| XueZhiKang/Week 4 | Comparison of XueZhiKang With Simvastatin of Physical Activity Level | Moderate level at baseline and week 4 | 15 participants |
Other Pre-specified
Treatment Adherence at Week 4 in Simvastatin- and Xuezhikang-group
We counted the total number of pills that were dispensed to the participants at baseline and the total number of pills that were taken by participants at week 4.
Time frame: Measured at baseline and week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simvastatin/Baseline | Treatment Adherence at Week 4 in Simvastatin- and Xuezhikang-group | 462 number of pills |
| Simvastatin/Week 4 | Treatment Adherence at Week 4 in Simvastatin- and Xuezhikang-group | 462 number of pills |
| XueZhiKang/Baseline | Treatment Adherence at Week 4 in Simvastatin- and Xuezhikang-group | 3024 number of pills |
| XueZhiKang/Week 4 | Treatment Adherence at Week 4 in Simvastatin- and Xuezhikang-group | 3024 number of pills |