Type IIa and IIb Hypercholesterolaemia
Conditions
Keywords
dyslipidemia
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Rosuvastatin 5 mg as an hypercholesterolemia treatment comparatively at 2 other statins: Pravastatin 40 mg and Atorvastatin 10 mg. Treatment efficacy will be evaluated by the percentage of LDL-C variation after 8 weeks of treatment.
Interventions
DRUGRosuvastatin
5mg oral
DRUGPravastatin
40mg oral
DRUGAtorvastatin
10mg oral
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* subjects presenting type IIa or IIb primary hypercholesterolaemia diagnosed for at least 3 months, in a context of primary prevention with at least two associated cardiovascular risk factors and: (i)either naive to all lipid-lowering therapy, (ii)or treated with a statin (treatment ongoing or stopped during the previous 8 weeks)
Exclusion criteria
* homozygous or heterozygous familial hypercholesterolaemia * hypertriglyceridaemia (TG ≥ 4 g/l) * subjects at high cardiovascular risk according to the AFSSAPS 2005 definition (coronary artery disease or history of documented vascular disease, high cardiovascular risk type 2 diabetes, subject in primary prevention with a 10-year CHD risk \> 20%) * history of adverse events or hypersensitivity to an HMG Co-A reductase inhibitor (particularly a history of myopathy) * concomitant use of any drugs not authorized during the study * active liver disease with elevation of serum transaminases (ASAT, ALAT) more than twice the upper limit of normal * CPK more than 3 times the upper limit of normal * moderate or severe renal failure (creatinine clearance \< 6 ml/min) * poorly controlled hypothyroidism; poorly controlled hypertension (DBP \> 95 mm Hg and/or SBP \> 180 mm Hg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Low Density Lipoprotein Cholesterol (LDL-C) Level After 8 Weeks | Change from baseline and after 8 weeks of treatment | To compare the percentages of LDL-C level variation. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Percentage of Patients Reaching the LDL-C Goal, in Relation to the Number of Risk Factors, According to the French Agency for the Safety of Health Products (AFSSAPS) 2005 Guidelines for the Management of Dyslipidaemic Patients | Not done | Not done. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| Compare the Percentage of Total Cholesterol Variation From Baseline and After 8 Weeks of Treatment | from baseline and after 8 weeks of treatment | To compare the percentage of total cholesterol variation taking baseline value as a reference. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| Compare the Percentage of HDL-C (High Density Lipoprotein Cholesterol) Variation From Baseline and After 8 Weeks of Treatment | After 8 weeks of treatment | Compare the percentage of HDL-C (High Density Lipoprotein Cholesterol) variation taking baseline value as a reference and after 8 weeks of treatment. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| Compare the Percentage of Variation From Baseline Triglycerides Values and After 8 Weeks | Baseline and after 8 weeks of treatment | To compare the percentage of variation from baseline triglycerides values and after 8 weeks. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| Compare the Percentage of Variation From Baseline Apolipoprotein B/Apolipoprotein A1 Ratio and After 8 Weeks of Treatment | baseline and after 8 weeks of treatment | To Compare the percentage of variation from baseline Apolipoprotein B/Apolipoprotein A1 ratio and after 8 weeks of treatment. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| To Compare the Percentage of Patients Reaching the Overall LDL-C Goal According to the French Agency for the Safety of Health Products (AFSSAPS) 2005 Guidelines for the Management of Dyslipidaemic Patients | Not done | Not done. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| Compare the Percentage of Variation of Phospholipase A2 (PLA2) | from baseline and after 8 weeks of treatment | To Compare the percentage of variation of phospholipase A2 (PLA2) taking baseline value as a reference. As the recruitment target was not reached at the date initially planned, and view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
| Compare the Numbers of Patients Achieving the LDL-C Goal According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) ATP III) Guidelines for the Management of Dyslipidaemic Patients | from baseline and after 8 weeks of treatment | To Compare numbers of patients achieving the LDL-C goal according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP). As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data. The percentage of patients achieving the NCEP-ATP III LDL-C goal. ATP III is categorized into 3 risk categories:(1) established CHD and CHD risk equivalents(2) multiple risk factors(3) zero to one (0-1) risk factor |
| Compare the Numbers of Patients Achieving the LDL-C Goal According to the European Atherosclerosis Society (EAS) Guidelines for the Management of Dyslipidaemic Patients | — | Not done. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data. |
| To Evaluate Clinical and Laboratory Safety | duration of study | Serious Adverse Event and Adverse Event reported throughout the study |
| Compare the Percentage of Variation of C-reactive Protein (CRP) | baseline and after 8 weeks of treatment | To compare the percentage of variation of C-reactive protein (CRP) taking baseline values as reference. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data |
Countries
France
Participant flow
Recruitment details
Patients were recruited by general practitioner. First patient included: 12 October 2007 Last patient terminated the study: 04 October 2008
Pre-assignment details
This French multicentre, randomized double-blind study was conducted on three parallel arms. The 14-week study comprised 3 visits: a screening visit (week 0, V1), a randomization and treatment allocation visit (week 6, V2) and an evaluation visit (week 14, V3). Patients were randomized at V2 and were treated for a period of 8 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Initial Phase Initial phase (between V1 and V2) | 0 |
| Atorvastatin Atorvastatin 10 mg | 104 |
| Pravastatin Pravastatin 40 mg | 103 |
| Rosuvastatin Rosuvastatin 5 mg | 110 |
| Total | 317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Initial Phase | Protocol Violation | 347 | 0 | 0 | 0 |
| Initial Phase | Withdrawal by Subject | 4 | 0 | 0 | 0 |
| Treatment Phase | Adverse Event | 0 | 3 | 2 | 4 |
| Treatment Phase | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Treatment Phase | patient did not take pravastatin | 0 | 0 | 1 | 0 |
| Treatment Phase | Pregnancy | 0 | 0 | 1 | 0 |
| Treatment Phase | Protocol Violation | 0 | 1 | 6 | 2 |
| Treatment Phase | Withdrawal by Subject | 0 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Atorvastatin | Pravastatin | Rosuvastatin | Total |
|---|---|---|---|---|
| Age, Continuous | 57.31 years STANDARD_DEVIATION 10.59 | 57.23 years STANDARD_DEVIATION 10.8 | 57.04 years STANDARD_DEVIATION 9.32 | 57.18 years STANDARD_DEVIATION 9.95 |
| Gender Female | 49 Participants | 55 Participants | 46 Participants | 150 Participants |
| Gender Male | 55 Participants | 48 Participants | 64 Participants | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 317 | 5 / 97 | 7 / 92 | 5 / 103 |
| serious Total, serious adverse events | 2 / 317 | 4 / 97 | 1 / 92 | 0 / 103 |
Outcome results
Primary
Change in Low Density Lipoprotein Cholesterol (LDL-C) Level After 8 Weeks
To compare the percentages of LDL-C level variation. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: Change from baseline and after 8 weeks of treatment
Population: 92 patients completed the study in the Pravastatin group, nevertheless, primary and secondary outcome measures are described on 91 patients in the Pravastatin arm due to one missing data in this group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Change in Low Density Lipoprotein Cholesterol (LDL-C) Level After 8 Weeks | -39.4 percentage of LDL-C decrease | Standard Deviation 13.77 |
| Pravastatin | Change in Low Density Lipoprotein Cholesterol (LDL-C) Level After 8 Weeks | -30.3 percentage of LDL-C decrease | Standard Deviation 15.43 |
| Rosuvastatin | Change in Low Density Lipoprotein Cholesterol (LDL-C) Level After 8 Weeks | -37.6 percentage of LDL-C decrease | Standard Deviation 17.96 |
Secondary
Compare the Numbers of Patients Achieving the LDL-C Goal According to the European Atherosclerosis Society (EAS) Guidelines for the Management of Dyslipidaemic Patients
Not done. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data.
Secondary
Compare the Numbers of Patients Achieving the LDL-C Goal According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) ATP III) Guidelines for the Management of Dyslipidaemic Patients
To Compare numbers of patients achieving the LDL-C goal according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP). As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data. The percentage of patients achieving the NCEP-ATP III LDL-C goal. ATP III is categorized into 3 risk categories:(1) established CHD and CHD risk equivalents(2) multiple risk factors(3) zero to one (0-1) risk factor
Time frame: from baseline and after 8 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin | Compare the Numbers of Patients Achieving the LDL-C Goal According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) ATP III) Guidelines for the Management of Dyslipidaemic Patients | 42 Participants |
| Pravastatin | Compare the Numbers of Patients Achieving the LDL-C Goal According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) ATP III) Guidelines for the Management of Dyslipidaemic Patients | 22 Participants |
| Rosuvastatin | Compare the Numbers of Patients Achieving the LDL-C Goal According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) ATP III) Guidelines for the Management of Dyslipidaemic Patients | 38 Participants |
Secondary
Compare the Percentage of HDL-C (High Density Lipoprotein Cholesterol) Variation From Baseline and After 8 Weeks of Treatment
Compare the percentage of HDL-C (High Density Lipoprotein Cholesterol) variation taking baseline value as a reference and after 8 weeks of treatment. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: After 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Compare the Percentage of HDL-C (High Density Lipoprotein Cholesterol) Variation From Baseline and After 8 Weeks of Treatment | 4.4 percentage of HDL-C increase | Standard Deviation 14.3 |
| Pravastatin | Compare the Percentage of HDL-C (High Density Lipoprotein Cholesterol) Variation From Baseline and After 8 Weeks of Treatment | 7.9 percentage of HDL-C increase | Standard Deviation 19.2 |
| Rosuvastatin | Compare the Percentage of HDL-C (High Density Lipoprotein Cholesterol) Variation From Baseline and After 8 Weeks of Treatment | 11.3 percentage of HDL-C increase | Standard Deviation 20.6 |
Secondary
Compare the Percentage of Total Cholesterol Variation From Baseline and After 8 Weeks of Treatment
To compare the percentage of total cholesterol variation taking baseline value as a reference. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: from baseline and after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Compare the Percentage of Total Cholesterol Variation From Baseline and After 8 Weeks of Treatment | -28.6 percentage of total cholesterol decrease | Standard Deviation 11 |
| Pravastatin | Compare the Percentage of Total Cholesterol Variation From Baseline and After 8 Weeks of Treatment | -20.4 percentage of total cholesterol decrease | Standard Deviation 11.7 |
| Rosuvastatin | Compare the Percentage of Total Cholesterol Variation From Baseline and After 8 Weeks of Treatment | -25.2 percentage of total cholesterol decrease | Standard Deviation 14 |
Secondary
Compare the Percentage of Variation From Baseline Apolipoprotein B/Apolipoprotein A1 Ratio and After 8 Weeks of Treatment
To Compare the percentage of variation from baseline Apolipoprotein B/Apolipoprotein A1 ratio and after 8 weeks of treatment. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: baseline and after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Compare the Percentage of Variation From Baseline Apolipoprotein B/Apolipoprotein A1 Ratio and After 8 Weeks of Treatment | -30.9 percent. Apolipoprotein B/A1 decrease | Standard Deviation 14.7 |
| Pravastatin | Compare the Percentage of Variation From Baseline Apolipoprotein B/Apolipoprotein A1 Ratio and After 8 Weeks of Treatment | -26 percent. Apolipoprotein B/A1 decrease | Standard Deviation 13.5 |
| Rosuvastatin | Compare the Percentage of Variation From Baseline Apolipoprotein B/Apolipoprotein A1 Ratio and After 8 Weeks of Treatment | -31.9 percent. Apolipoprotein B/A1 decrease | Standard Deviation 17 |
Secondary
Compare the Percentage of Variation From Baseline Triglycerides Values and After 8 Weeks
To compare the percentage of variation from baseline triglycerides values and after 8 weeks. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: Baseline and after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Compare the Percentage of Variation From Baseline Triglycerides Values and After 8 Weeks | -19.2 percentage of triglycerides decrease | Standard Deviation 25 |
| Pravastatin | Compare the Percentage of Variation From Baseline Triglycerides Values and After 8 Weeks | -6.1 percentage of triglycerides decrease | Standard Deviation 31.6 |
| Rosuvastatin | Compare the Percentage of Variation From Baseline Triglycerides Values and After 8 Weeks | -8.7 percentage of triglycerides decrease | Standard Deviation 37 |
Secondary
Compare the Percentage of Variation of C-reactive Protein (CRP)
To compare the percentage of variation of C-reactive protein (CRP) taking baseline values as reference. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: baseline and after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Compare the Percentage of Variation of C-reactive Protein (CRP) | 37.3 percent of variation of C-reactive prot. | Standard Deviation 187.4 |
| Pravastatin | Compare the Percentage of Variation of C-reactive Protein (CRP) | 33.1 percent of variation of C-reactive prot. | Standard Deviation 184.2 |
| Rosuvastatin | Compare the Percentage of Variation of C-reactive Protein (CRP) | 15.2 percent of variation of C-reactive prot. | Standard Deviation 104.9 |
Secondary
Compare the Percentage of Variation of Phospholipase A2 (PLA2)
To Compare the percentage of variation of phospholipase A2 (PLA2) taking baseline value as a reference. As the recruitment target was not reached at the date initially planned, and view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: from baseline and after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Compare the Percentage of Variation of Phospholipase A2 (PLA2) | 5.6 percent of variation of phospholipase A2 | Standard Deviation 46.4 |
| Pravastatin | Compare the Percentage of Variation of Phospholipase A2 (PLA2) | 13 percent of variation of phospholipase A2 | Standard Deviation 73.6 |
| Rosuvastatin | Compare the Percentage of Variation of Phospholipase A2 (PLA2) | 2.9 percent of variation of phospholipase A2 | Standard Deviation 24.2 |
Secondary
To Compare the Percentage of Patients Reaching the LDL-C Goal, in Relation to the Number of Risk Factors, According to the French Agency for the Safety of Health Products (AFSSAPS) 2005 Guidelines for the Management of Dyslipidaemic Patients
Not done. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: Not done
Secondary
To Compare the Percentage of Patients Reaching the Overall LDL-C Goal According to the French Agency for the Safety of Health Products (AFSSAPS) 2005 Guidelines for the Management of Dyslipidaemic Patients
Not done. As the recruitment target was not reached at the date initially planned, and in view of the recruitment difficulties, AstraZeneca decided not to extend the patient recruitment period and to perform only a descriptive analysis of the data
Time frame: Not done
Secondary
To Evaluate Clinical and Laboratory Safety
Serious Adverse Event and Adverse Event reported throughout the study
Time frame: duration of study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Phase | To Evaluate Clinical and Laboratory Safety | 8 Adverse Events |
| Atorvastatin | To Evaluate Clinical and Laboratory Safety | 9 Adverse Events |
| Pravastatin | To Evaluate Clinical and Laboratory Safety | 8 Adverse Events |
| Rosuvastatin | To Evaluate Clinical and Laboratory Safety | 5 Adverse Events |