Elevated High-sensitivity C-Reactive Protein (hsCRP)
Conditions
Keywords
Primary prevention, Cardiovascular disease, Statin therapy, C-reactive protein
Brief summary
The purpose of this study is to determine the safety and effectiveness of long-term therapy with rosuvastatin compared with a placebo, and to evaluate whether treatment with rosuvastatin might be effective in reducing the risk of major cardiovascular events.
Detailed description
AstraZeneca announced it has decided to stop the CRESTOR JUPITER clinical study early based on a recommendation from an Independent Data Monitoring Board and the JUPITER Steering Committee, which met on March 29, 2008. The study will be stopped early because there is unequivocal evidence of a reduction in cardiovascular morbidity and mortality amongst patients who received CRESTOR when compared to placebo.
Interventions
DRUGRosuvastatin
Oral
OTHERPlacebo
Oral
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men 50 years or older, women 60 years or older * Low to normal levels of low density lipoprotein (LDL) cholesterol (\< 130mg/dL) * Elevated levels of C-Reactive Protein (CRP) \> 2.0 mg/L
Exclusion criteria
* History of cardiovascular or cerebrovascular events * Active liver disease * Diabetes mellitus * Uncontrolled hypertension or hypothyroidism * History of certain malignancies * Chronic inflammatory conditions * History of alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Major Cardiac Event (Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization Due to Unstable Angina or Arterial Revascularization) | up to 5 years | Days from randomization to the first of CV death, stroke, MI, hospitalization for unstable angina or arterial revascularization. If no event, censoring occurs at earliest of termination date or efficacy cut-off date of 30 Mar 2008. Events were adjudicated by an endpoint committee. Kaplan-Meier estimate of the mean |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death Due to Any Cause | up to 5 years | Days from randomization to death. If no death then censoring occurs at earliest of termination date or efficacy cutoff date of 30 Mar 2008. Kaplan-Meier estimate of the mean |
| Time to Non-cardiovascular Death | up to 5 years | Days from randomization to death from a non-cardiovascular cause. If no event, then censoring occurs at earliest of termination date or efficacy cutoff date of 30 Mar 2008. Events were adjudicated by an endpoint committee. Kaplan-Meier estimate of the mean |
| Time to Development of Diabetes Mellitus | up to 5 years | Days from randomization until development of diabetes. If no diabetes was developed censoring occurred at termination date. Kaplan-Meier estimate of the mean |
| Time to Venous Thromboembolic Event | up to 5 years | Time from randomization to the first venous thromboembolic event. Kaplan-Meier estimate of the mean |
| Time to Bone Fracture | Up to 5 years | Days from randomization until bone fracture. If no event, then censoring occurs at earliest of termination date or efficacy cutoff date of 30 Mar 2008. Kaplan-Meier estimate of the mean |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica, Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands, Norway, Panama, Poland, Puerto Rico, Romania, Russia, South Africa, Switzerland, United Kingdom, United States, Uruguay, Venezuela
Participant flow
Recruitment details
The first subject was enrolled on 05 February 2003. The last subject completed on 20 August 2008. Study subjects were randomized at 1348 centers in 26 countries. Enrolled subjects participated in an initial 4-week, run-in phase and received placebo therapy.
Pre-assignment details
If found eligible for the main study on the basis of appropriate levels of baseline Low Density Lipoprotein (LDL), High-sensitivity C-Reactive Protein (hsCRP), and run-in phase compliance (\>80% of pills taken), subjects were randomized to either rosuvastatin 20 mg or placebo once daily
Participants by arm
| Arm | Count |
|---|---|
| Rosuvastatin Rosuvastatin 20 mg once daily | 8,901 |
| Placebo Placebo once daily | 8,901 |
| Total | 17,802 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 100 | 99 |
| Overall Study | Lost to Follow-up | 28 | 22 |
| Overall Study | No information chacked on CaseReportForm | 90 | 84 |
| Overall Study | Physician Decision | 13 | 17 |
| Overall Study | Protocol Violation | 4 | 4 |
| Overall Study | Withdrawal by Subject | 458 | 489 |
Baseline characteristics
| Characteristic | Rosuvastatin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 7.64 | 66.1 years STANDARD_DEVIATION 7.8 | 66.1 years STANDARD_DEVIATION 7.72 |
| Sex: Female, Male Female | 3426 Participants | 3375 Participants | 6801 Participants |
| Sex: Female, Male Male | 5475 Participants | 5526 Participants | 11001 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3,170 / 8,864 | 3,228 / 8,869 |
| serious Total, serious adverse events | 1,216 / 8,864 | 1,205 / 8,869 |
Outcome results
Primary
Time to Major Cardiac Event (Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization Due to Unstable Angina or Arterial Revascularization)
Days from randomization to the first of CV death, stroke, MI, hospitalization for unstable angina or arterial revascularization. If no event, censoring occurs at earliest of termination date or efficacy cut-off date of 30 Mar 2008. Events were adjudicated by an endpoint committee. Kaplan-Meier estimate of the mean
Time frame: up to 5 years
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Time to Major Cardiac Event (Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization Due to Unstable Angina or Arterial Revascularization) | 1646.4 Days | Standard Error 2.76 |
| Placebo | Time to Major Cardiac Event (Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization Due to Unstable Angina or Arterial Revascularization) | 1578.3 Days | Standard Error 3.49 |
p-value: <0.000195% CI: [0.46, 0.69]Regression, Cox
Secondary
Time to Bone Fracture
Days from randomization until bone fracture. If no event, then censoring occurs at earliest of termination date or efficacy cutoff date of 30 Mar 2008. Kaplan-Meier estimate of the mean
Time frame: Up to 5 years
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Time to Bone Fracture | 1662.7 Days | Standard Error 3.35 |
| Placebo | Time to Bone Fracture | 1546.9 Days | Standard Error 2.78 |
p-value: 0.54895% CI: [0.88, 1.28]Regression, Cox
Secondary
Time to Death Due to Any Cause
Days from randomization to death. If no death then censoring occurs at earliest of termination date or efficacy cutoff date of 30 Mar 2008. Kaplan-Meier estimate of the mean
Time frame: up to 5 years
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Time to Death Due to Any Cause | 1543.3 days | Standard Error 2.48 |
| Placebo | Time to Death Due to Any Cause | 1619.1 days | Standard Error 3.1 |
p-value: <0.02195% CI: [0.67, 0.97]Regression, Cox
Secondary
Time to Development of Diabetes Mellitus
Days from randomization until development of diabetes. If no diabetes was developed censoring occurred at termination date. Kaplan-Meier estimate of the mean
Time frame: up to 5 years
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Time to Development of Diabetes Mellitus | 1687.0 Days | Standard Error 3.92 |
| Placebo | Time to Development of Diabetes Mellitus | 1517.0 Days | Standard Error 2.46 |
p-value: <0.01595% CI: [1.05, 1.53]Regression, Cox
Secondary
Time to Non-cardiovascular Death
Days from randomization to death from a non-cardiovascular cause. If no event, then censoring occurs at earliest of termination date or efficacy cutoff date of 30 Mar 2008. Events were adjudicated by an endpoint committee. Kaplan-Meier estimate of the mean
Time frame: up to 5 years
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Time to Non-cardiovascular Death | 1558.5 Days | Standard Error 1.9 |
| Placebo | Time to Non-cardiovascular Death | 1640.5 Days | Standard Error 2.44 |
p-value: <0.17295% CI: [0.65, 1.08]Regression, Cox
Secondary
Time to Venous Thromboembolic Event
Time from randomization to the first venous thromboembolic event. Kaplan-Meier estimate of the mean
Time frame: up to 5 years
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Time to Venous Thromboembolic Event | 1147.4 Days | Standard Error 0.54 |
| Placebo | Time to Venous Thromboembolic Event | 1377.2 Days | Standard Error 1.05 |
p-value: 0.01895% CI: [0.35, 0.91]Regression, Cox