Cardiovascular Diseases, Dyslipidemias, Hypertriglyceridemia
Conditions
Keywords
Lipid Regulating Agents, Drug Therapy, cardiovascular diseases, hypertriglyceridemia, Hydroxymethylglutaryl-CoA Reductase Inhibitors, fenofibrate, Dyslipidemias, Combination
Brief summary
Atherogenic dyslipidemia includes patients who have coronary heart disease (CHD) or CHD risk equivalents, whose TG level is not adequately controlled after statin monotherapy. According to the published ESC/EAS consensus, fibrate is suggested to be added to this type of patient who has insufficient improvement. The purpose of the study is to evaluate the efficacy on lipid control and the safety of adding fenofibrate in patients on a background of statin treatment.
Detailed description
It is an open-label , single group, multi-center study. At around 30 investigate sites, 500 dyslipidemic Chinese patients with coronary heart disease (CHD) or CHD risk equivalent, whose TG ≥1.70 mmol/L (150mg/dl) and \<5.65mmol/L (500mg/dl) after at least 2 month statin monotherapy with standard dose will be enrolled. After at least 2 month statin monotherapy with standard dose, patients having high TG will be recruited and given statin-fenofibrate combination therapy for 8 weeks. Several lipid parameters and safety parameters will be compared between baseline, after 4 weeks treatment and after 8 weeks treatment. Primary efficacy endpoint is the percentage of TG decrease before and after 8 weeks treatment. Secondary endpoints on efficacy are the absolute change and the percent of change on TC, LDL-C, HDL-C, apoA1, apoB and apoB/apoA1 of baseline, after 4 weeks treatment and 8 weeks treatment, absolute change and percentage of change of hsCRP from baseline to 8 weeks of treatment. Second endpoints on safety is the incidence of AE/SAE, change on CK, ALT, AST, BUN and Cr before and after treatment and the number of clinical meaningful abnormal change defined as ALT or AST \>3ULN, or CK \>10ULN, or BUN \>1.5ULN or Cr \>1.5ULN. Other Arm type is a self comparator
Interventions
DRUGfenofibrate
Fenofibrate Capsule 200mg qd orally
Sponsors
Rundo International Pharmaceutical Research & Development Co.,Ltd.
Abbott
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. ≥18 years and \< 80 years, male or female 2. With at least one risk of coronary heart disease (CHD) \[medical history of myocardial infarction (MI) or coronary angiography shows coronary stenosis ≥ 50% or post percutaneous coronary intervention (PCI) or post coronary artery bypass grafting (CABG)\] or CHD risk equivalents, which comprise, * Other clinical forms of atherosclerotic disease (ischemic stroke, peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) * Type 2 Diabetes * Multiple risk factors that confer a 10-year risk for CHD \>20%. 3. ≥ 2 months statin monotherapy with standard dose (atorvastatin ≤20mg q.d. or rosuvastatin ≤10mg q.d. or simvastatin ≤40mg q.d. or pravastatin ≤40mg q.d. or pitavastatin ≤4mg q.d or fluvastatin ≤80mg q.d. or lovastatin ≤40mg q.d.) and plan to continue the previous type and dose of statin 4. Triglycerides (TG)≥1.70 mmol/L (150mg/dl) and TG\<5.65 mmol/L (500mg/dl) 5. Subject must be able to provide informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), on his or her own behalf, prior to any study-specific procedures.
Exclusion criteria
1. Hypersensitive to fenofibrate or to any of its excipients 2. Hepatic insufficiency \[alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2ULN (upper limit of normal)\] 3. Renal insufficiency \[Creatinine clearance rate (Ccr)\<60ml/min estimated from Cockcroft-Gault equation Ccr=(140-age)\*weight(Kg)\*0.85(if female)/\[0.818\*Cr (µmol/L)\] 4. Creatine kinase (CK) \> 2 ULN 5. Congenital galactosemia, glucose-galactose malabsorption syndrome or lactase deficiency 6. Hypothyroidism 7. Combination use of other non-statin lipid-regulating drugs such as fibrates, niacin and fish oil in previous 2 months 8. Combination use of drug with similar structure as Fenofibrate, especially ketoprofen 9. Combination use of oral anticoagulants 10. Pregnant or lactating woman 11. Other conditions at investigator's discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Triglyceride (TG) Change | Baseline and up to 8 weeks after intervention | Blood tests |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Low-density Lipoprotein Cholesterol | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum High-density Lipoprotein Cholesterol | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum Non-high-density Lipoprotein Cholesterol | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum Apolipoprotein A1 | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum Apolipoprotein B | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum Total Cholesterol | Baseline and up to 8 weeks after intervention | Blood tests |
| Change in Serum Aspartate Aminotransferase | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum Creatine Kinase | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum Creatinine | Baseline up to 8 weeks after intervention | Blood tests |
| Change in Serum High Sensitivity C-reactive Protein | Baseline and up to 8 weeks after intervention | Blood tests |
| Change in Serum Alanine Aminotransferase | Baseline up to 8 weeks after intervention | Blood tests |
Countries
China
Participant flow
Recruitment details
Dyslipidemic Chinese patients with CHD or CHD equivalent, whose TG ≥1.70 mmol/L and \<5.65mmol/L after at least 2 month statin monotherapy with standard dose were enrolled. After at least 2 month statin monotherapy with standard dose, patients having high TG were recruited and given statin-fenofibrate combination therapy for 8 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Fenofibrate Arm fenofibrate: Fenofibrate Capsule 200mg qd orally | 468 |
| Total | 468 |
Baseline characteristics
| Characteristic | Fenofibrate Arm |
|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 9.91 |
| diastolic blood pressure | 78.54 mmHg STANDARD_DEVIATION 8.97 |
| Sex: Female, Male Female | 194 Participants |
| Sex: Female, Male Male | 274 Participants |
| Systolic blood pressure | 130.93 mmHg STANDARD_DEVIATION 12.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 492 |
| serious Total, serious adverse events | 7 / 492 |
Outcome results
Primary
Percentage of Triglyceride (TG) Change
Blood tests
Time frame: Baseline and up to 8 weeks after intervention
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Percentage of Triglyceride (TG) Change | -38.12 percentage of TG change | Standard Deviation 33.92 |
Secondary
Change in Serum Alanine Aminotransferase
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Safety set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Arm | Change in Serum Alanine Aminotransferase | 0.00 percentage of ALT change |
Secondary
Change in Serum Apolipoprotein A1
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Change in Serum Apolipoprotein A1 | 12.41 percentage of apoA1 change | Standard Deviation 28.74 |
Secondary
Change in Serum Apolipoprotein B
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Change in Serum Apolipoprotein B | 2.42 percentage of apoB change | Standard Deviation 50.48 |
Secondary
Change in Serum Aspartate Aminotransferase
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Safety set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Arm | Change in Serum Aspartate Aminotransferase | 10.91 percentage of AST change |
Secondary
Change in Serum Creatine Kinase
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Safety set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Arm | Change in Serum Creatine Kinase | 8.02 percentage of CK change |
Secondary
Change in Serum Creatinine
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Safety set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Arm | Change in Serum Creatinine | 12.99 percentage of Creatinine change |
Secondary
Change in Serum High-density Lipoprotein Cholesterol
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Change in Serum High-density Lipoprotein Cholesterol | 17.40 percentage of HDL-C change | Standard Deviation 32.62 |
Secondary
Change in Serum High Sensitivity C-reactive Protein
Blood tests
Time frame: Baseline and up to 8 weeks after intervention
Secondary
Change in Serum Low-density Lipoprotein Cholesterol
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Change in Serum Low-density Lipoprotein Cholesterol | 14.91 percentage of LDL-C change | Standard Deviation 39.8 |
Secondary
Change in Serum Non-high-density Lipoprotein Cholesterol
Blood tests
Time frame: Baseline up to 8 weeks after intervention
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Change in Serum Non-high-density Lipoprotein Cholesterol | -1.30 percentage of Non-HDL-C change | Standard Deviation 28.26 |
Secondary
Change in Serum Total Cholesterol
Blood tests
Time frame: Baseline and up to 8 weeks after intervention
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibrate Arm | Change in Serum Total Cholesterol | 2.75 percentage of TC change | Standard Deviation 24.75 |