CRESTOR Athero Imaging Head to Head IVUS Study

Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00620542

Acronym

SATURN

Enrollment

2333

Registered

2008-02-21

Start date

2008-01-31

Completion date

2011-06-30

Last updated

2012-07-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Atherosclerosis

Keywords

Coronary artery disease

Brief summary

A 104-week, randomized, double-blind, parallel group, multi-center Phase IIIb study comparing the effects of treatment with rosuvastatin 40 mg or atorvastatin 80 mg on atherosclerotic disease burden as measured by intravascular ultrasound in patients with coronary artery disease.

Interventions

DRUGRosuvastatin

capsule, oral, once daily

DRUGAtorvastatin

capsule, oral, one daily

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 75 Years

Healthy volunteers

Inclusion criteria

* Clinical indication for coronary angiography * Angiographic evidence of Coronary Artery Disease (CAD), as defined by at least 1 lesion in a native coronary artery that has \>20% reduction in lumen diameter by visual estimation * Left main coronary artery must have \<=50% reduction in lumen diameter by visual estimation * LDL-C \>100 mg/dL (2.6 mmol/L) for patients with no statin therapy in the past 4 weeks; LDL-C \>80mg/dL (2.08mmol/L) for patients on therapy in the past 4 weeks

Exclusion criteria

* Use of certain lipid-lowering medication for more than 3 months within the previous 12 months. Longer periods of treatment are not permitted because of the potential effects of such therapy on coronary atherosclerosis. * Patients who have symptoms consistent with moderate or greater severity of Congestive Heart Failure (CHF). * Clinically significant heart disease which, in the opinion of the Principal Investigator (or designee), is likely to require coronary bypass surgery, cardiac transplantation, surgical repair and/or replacement during the course of the study

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to End of Study (Week 104) in Percent Atheroma Volume (PAV)	End of study (Week 104)	Change in PAV computed as PAV(Week 104)-PAV(baseline) where PAV is calculated as: \[sum(EEMcsa-LUMENcsa)/sum EEMcsa\]\*100 where EEMcsa is the cross-sectional area of the external elastic membrane and LUMENcsa is the cross-sectional area of the lumen, as measured by intravascular ultrasound IVUS of a coronary artery in patients with CAD.

Secondary

Measure	Time frame	Description
LDL-C Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Numbers of Patients Showing Regression in PAV	End of study (Week 104)	Regression defined as a change from baseline in PAV \< 0
Change From Baseline to End of Study (Week 104) in Total Atheroma Volume (TAV)	End of study (Week 104)	Change in TAV, as measured by IVUS, computed as TAV(Week 104)-TAV(baseline) where TAV is the sum(EEMcsa-LUMENcsa)/n. n is the number of cross-sections measured. TAV for each patient is calculated as the average area of atheroma per cross-section multiplied by the median number of cross-sections measured for all patients in the analysis population.
Numbers of Patients Showing Regression in TAV	End of study (Week 104)	Regression defined as a change from baseline in TAV \< 0
HDL-C Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Triglycerides Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Non-HDL-C Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Total Cholesterol Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Total Cholesterol/HDL-C Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Non-HDL-C/HDL-C Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Apolipoprotein B Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Apolipoprotein A-1 Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
Apoliprotein B/Apolipoprotein A-1 Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
VLDL-C During the 104 Week Treatment Period	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.
LDL-C/HDL-C Blood Level	104 weeks	Time-weighted average is calculated as the lipid value times the number of days since last lipid assessment, summed for all and divided by the number of days from Part B randomization to date of the last lipid evaluation.

Countries

Argentina, Australia, Belgium, Brazil, Canada, France, Hungary, Italy, Mexico, Netherlands, Poland, Russia, Spain, United States

Participant flow

Recruitment details

2333 Coronary Artery Disease (CAD) patients with clinical indication for coronary angiography were randomized to Part A, the 2-week run-in period. Of these, 1578 patients were treated and 1385 completed Part A. The 1385 patients completing Part A were then randomized to Part B the core study period of 104 weeks of treatment.

Pre-assignment details

Angiography was performed to determine if patients were qualified to continue in the study based on protocol-specified angiographic criteria. Patients who satisfied all inclusion and exclusion criteria had an Intravascular Ultrasound (IVUS) performed within 2 weeks of the qualifying angiography.

Participants by arm

Arm	Count
Rosuvastatin 40 mg 2 years	520
Atorvastatin 80 mg 2 years	519
Total	1,039

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Part A (Run-in - 2 Weeks)	Adverse Event	12	15	0	0
Part A (Run-in - 2 Weeks)	IVUS not available	4	4	0	0
Part A (Run-in - 2 Weeks)	Lost to Follow-up	7	6	0	0
Part A (Run-in - 2 Weeks)	Protocol Violation	406	409	0	0
Part A (Run-in - 2 Weeks)	Safety reasons	0	1	0	0
Part A (Run-in - 2 Weeks)	Withdrawal by Subject	43	40	0	0
Part B (2 Year Core Study)	Adverse Event	0	0	46	49
Part B (2 Year Core Study)	IVUS not available	0	0	3	2
Part B (2 Year Core Study)	Lost to Follow-up	0	0	20	9
Part B (2 Year Core Study)	Protocol Violation	0	0	3	5
Part B (2 Year Core Study)	Safety reasons	0	0	2	3
Part B (2 Year Core Study)	Study specific discontinuation criteris	0	0	6	6
Part B (2 Year Core Study)	Withdrawal by Subject	0	0	55	54

Baseline characteristics

Characteristic	Rosuvastatin 40 mg	Atorvastatin 80 mg	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	118 Participants	124 Participants	242 Participants
Age, Categorical Between 18 and 65 years	402 Participants	395 Participants	797 Participants
Age Continuous Age (yrs) at Week 0	57.4 years STANDARD_DEVIATION 8.6	57.9 years STANDARD_DEVIATION 8.5	57.6 years STANDARD_DEVIATION 8.55
Sex: Female, Male Female	141 Participants	133 Participants	274 Participants
Sex: Female, Male Male	379 Participants	386 Participants	765 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	0 / 783	0 / 795	210 / 691	213 / 689
serious Total, serious adverse events	21 / 783	25 / 795	194 / 691	168 / 689

Outcome results

Primary

Change From Baseline to End of Study (Week 104) in Percent Atheroma Volume (PAV)

Change in PAV computed as PAV(Week 104)-PAV(baseline) where PAV is calculated as: \[sum(EEMcsa-LUMENcsa)/sum EEMcsa\]\*100 where EEMcsa is the cross-sectional area of the external elastic membrane and LUMENcsa is the cross-sectional area of the lumen, as measured by intravascular ultrasound IVUS of a coronary artery in patients with CAD.

Time frame: End of study (Week 104)