Rosuvastatin in the Long-term Treatment of Hypercholesterolaemic Subjects With Coronary Heart Disease

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00329160
• Collaborator: Shionogi (Industry)
• Enrollment: 214
• Locations: 27
• Duration (Months): 36
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate that 76 weeks of treatment with rosuvastatin calcium 2.5-20 mg results in no progression of coronary artery atherosclerotic volume as measured by intravascular ultrasonography (IVUS) imaging in hypercholesterolaemic subjects with coronary heart disease (CHD).

Condition or Disease	Intervention/Treatment	Phase
Hypercholesteremia	Drug: Rosuvastatin; Drug: HMG CoA inhibitor	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 214 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Evaluate the Efficacy and Safety of Rosuvastatin in the Long-term Treatment of Hypercholesterolaemic Subjects With Coronary Heart Disease as Measured by Intravascular Ultrasonography
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline (Before the Start of Rosuvastatin Treatment) to Week 76 in the Plaque Volume (PV) [Baseline and 76 weeks]

   Plaque volume will be assessed by volumetric analysis with the echoPlaque2 system (Indec Systems Inc). Baseline and follow-up IVUS images will be reviewed side-by-side on a display, and the target segment selected. The target segment to be monitored will be determined in a non-PCI site (>5 mm proximal or distal to the PCI site) with a reproducible index such as side branches, calcifications, or stent edges.

Secondary Outcome Measures

1. Change From Baseline to Week 76 in Plaque Volume (PV) in the Target Lesion [Baseline - 76Weeks]

   Target Lesion indicates Coronary plaque composition of culprit lesions.

2. Percent Change From Baseline to Specified Measurement Time Points in Low-density Lipoprotein （LDL-C） [Baseline - 76Weeks]

3. Percent Change in High-sensitivity C-reactive Protein (HS-CRP) From Baseline to Specified Measurement Time Points [Baseline - 76Weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed written informed consent,

• 20 to 75 years old,

• Plan to undergo coronary angiography (CAG) or Percutaneous coronary intervention (PCI) and LDL-C ≥ 140 mg/dL (untreated patients) or LDL-C ≥ 100 mg/dL (treated patients)

Exclusion Criteria:

• Acute myocardial infarction within 72 hours after the onset,

• Heart failure of New York Heart Association (NYHA) Class III or above,

• Serious arrhythmia,

• Being treated with LDL-apheresis

• History of serious reaction or hypersensitivity to other HMG-CoA reductase inhibitors.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Gifu		Japan
2	Research Site	Hamada		Japan
3	Research Site	Hiroshima		Japan
4	Research Site	Ichinomiya		Japan
5	Research Site	Inba-mura		Japan
6	Research Site	Izumisano		Japan
7	Research Site	Izumi		Japan
8	Research Site	Izumo		Japan
9	Research Site	Kagoshima		Japan
10	Research Site	Kanazawa		Japan
11	Research Site	Kasuga		Japan
12	Research Site	Kobe		Japan
13	Research Site	Komaki		Japan
14	Research Site	Konan-cho		Japan
15	Research Site	Kumamoto		Japan
16	Research Site	Kurume		Japan
17	Research Site	Kyoto		Japan
18	Research Site	Omiya		Japan
19	Research Site	Osaka		Japan
20	Research Site	Sapporo		Japan
21	Research Site	Shinjo		Japan
22	Research Site	Shunan		Japan
23	Research Site	Suita		Japan
24	Research Site	Tokyo		Japan
25	Research Site	Ube		Japan
26	Research Site	Yamaguchi		Japan
27	Research Site	Yokohama		Japan

Sponsors and Collaborators

• AstraZeneca
• Shionogi

Investigators

• Principal Investigator: Masunori Matsuzaki, MD, Yamaguchi University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00329160
• Other Study ID Numbers: D3565L00002; 0407E1841
• First Posted: May 24, 2006
• Last Update Posted: Aug 31, 2011
• Last Verified: Aug 1, 2011

• Additional relevant MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Hypercholesterolemia; Rosuvastatin Calcium

Study Results

Participant Flow

Pre-assignment Detail	Observation Period :Prior to study-related activities, all subjects will sign an informed consent form. IVUS and CAG is performed prior Treatment Treatment Period: Eligible patients started treatment; rosuvastatin 2.5 mg once daily; those whose LDL-C remained >80 mg/dl after 4 wks of treatment, the dose can be titrated to a maximum of 20 mg/day

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
Period Title: Overall Study
STARTED	214
Observation Period	214
Treatment Period	214
COMPLETED	126
NOT COMPLETED	88

Baseline Characteristics

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
Overall Participants	126
Age (years) [Mean (Standard Deviation) ]
Years	62.6 (7.7)
Sex: Female, Male (Count of Participants)
Female	30 23.8%
Male	96 76.2%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline (Before the Start of Rosuvastatin Treatment) to Week 76 in the Plaque Volume (PV)
Description	Plaque volume will be assessed by volumetric analysis with the echoPlaque2 system (Indec Systems Inc). Baseline and follow-up IVUS images will be reviewed side-by-side on a display, and the target segment selected. The target segment to be monitored will be determined in a non-PCI site (>5 mm proximal or distal to the PCI site) with a reproducible index such as side branches, calcifications, or stent edges.
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
Measure Participants	126
Mean (Standard Deviation) [Percent Change]	14.1 (-5.066)

2. Secondary Outcome

Title	Change From Baseline to Week 76 in Plaque Volume (PV) in the Target Lesion
Description	Target Lesion indicates Coronary plaque composition of culprit lesions.
Time Frame	Baseline - 76Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
Measure Participants	126
Mean (Standard Deviation) [mg/dL]	12.074 (-5.259)

3. Secondary Outcome

Title	Percent Change From Baseline to Specified Measurement Time Points in Low-density Lipoprotein （LDL-C）
Time Frame	Baseline - 76Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
Measure Participants	126
Mean (Standard Deviation) [Percent change]	16.9 (-38.6)

4. Secondary Outcome

Title	Percent Change in High-sensitivity C-reactive Protein (HS-CRP) From Baseline to Specified Measurement Time Points
Time Frame	Baseline - 76Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
Measure Participants	126
Mean (Standard Deviation) [Percent change]	18.1 (291.3)

Adverse Events

Arm/Group Title	Rosuvastatin
Arm/Group Description	rosuvastatin 2.5 mg once daily; in those whose LDL-C remained >80 mg/dl after 4 weeks of treatment, the dosage could be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan. Subjects attended follow-up visits every 4 weeks over 76 weeks after starting treatment with rosuvastatin.
All Cause Mortality
	Rosuvastatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rosuvastatin
	Affected / at Risk (%)	# Events
Total	98/213 (46%)
Blood and lymphatic system disorders
Anaemia	1/213 (0.5%)
Cardiac disorders
Acute Myocardial Infarction	1/213 (0.5%)
Angina Pectoris	7/213 (3.3%)
Angina Unstable	1/213 (0.5%)
Atrioventricular Block	1/213 (0.5%)
Cardiac Failure	1/213 (0.5%)
Cardiac Failure Acute	1/213 (0.5%)
Cardiac Failure Congestive	2/213 (0.9%)
Coronary Artery Perforation	1/213 (0.5%)
Coronary Artery Stenosis	21/213 (9.9%)
Prinzmetal Angina	2/213 (0.9%)
Eye disorders
Cataract	1/213 (0.5%)
Gastrointestinal disorders
Enterocolitis	1/213 (0.5%)
Melaena	1/213 (0.5%)
Rectal Ulcer	1/213 (0.5%)
General disorders
Oedema Peripheral	1/213 (0.5%)
Puncture Site Haemorrhage	1/213 (0.5%)
Pyrexia	2/213 (0.9%)
Hepatobiliary disorders
Cholelithiasis	1/213 (0.5%)
Hepatic Function Abnormal	2/213 (0.9%)
Liver Disorder	1/213 (0.5%)
Infections and infestations
Bronchopneumonia	1/213 (0.5%)
Cellulitis	1/213 (0.5%)
Filariasis	1/213 (0.5%)
Liver Abscess	1/213 (0.5%)
Injury, poisoning and procedural complications
Brain Contusion	1/213 (0.5%)
Coronary Artery Restenosis	2/213 (0.9%)
Femoral Neck Fracture	1/213 (0.5%)
In-Stent Coronary Artery Restenosis	2/213 (0.9%)
Stent Occlusion	1/213 (0.5%)
Subdural Haematoma	2/213 (0.9%)
Alanine Aminotransferase Increased	1/213 (0.5%)
Aspartate Aminotransferase Increased	1/213 (0.5%)
Blood Alkaline Phosphatase Increased	1/213 (0.5%)
Blood Bilirubin Increased	1/213 (0.5%)
Blood Pressure Decreased	1/213 (0.5%)
C-Reactive Protein Increased	2/213 (0.9%)
Gamma-Glutamyltransferase Increased	1/213 (0.5%)
Glycosylated Haemoglobin Increased	1/213 (0.5%)
Neutrophil Count Decreased	1/213 (0.5%)
Platelet Count Decreased	1/213 (0.5%)
Metabolism and nutrition disorders
Diabetes Mellitus	2/213 (0.9%)
Musculoskeletal and connective tissue disorders
Back Pain	1/213 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile Duct Cancer	1/213 (0.5%)
Large Intestine Carcinoma	1/213 (0.5%)
Ovarian Cancer	1/213 (0.5%)
Prostate Cancer	2/213 (0.9%)
Small Cell Lung Cancer Stage Unspecified	1/213 (0.5%)
Nervous system disorders
Cerebral Haemorrhage	1/213 (0.5%)
Cerebral Infarction	2/213 (0.9%)
Dysarthria	1/213 (0.5%)
Facial Palsy	1/213 (0.5%)
Hemiparesis	1/213 (0.5%)
Loss Of Consciousness	1/213 (0.5%)
Thalamus Haemorrhage	1/213 (0.5%)
Visual Field Defect	1/213 (0.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/213 (0.5%)
Dyspnoea	1/213 (0.5%)
Skin and subcutaneous tissue disorders
Haemorrhage Subcutaneous	1/213 (0.5%)
Surgical and medical procedures
Arterial Bypass Operation	1/213 (0.5%)
Coronary Angioplasty	1/213 (0.5%)
Other (Not Including Serious) Adverse Events
	Rosuvastatin
	Affected / at Risk (%)	# Events
Total	588/214 (274.8%)
Gastrointestinal disorders
Constipation	14/214 (6.5%)
Dental Caries	11/214 (5.1%)
Diarrhoea	12/214 (5.6%)
Infections and infestations
Nasopharyngitis	69/214 (32.2%)
Alanine Aminotransferase Increased	38/214 (17.8%)
Aspartate Aminotransferase Increased	28/214 (13.1%)
Blood Alkaline Phosphatase Increased	20/214 (9.3%)
Blood Creatine Phosphokinase Increased	43/214 (20.1%)
Blood Pressure Increased	22/214 (10.3%)
Blood Urine Present	33/214 (15.4%)
C-Reactive Protein Increased	16/214 (7.5%)
Gamma-Glutamyltransferase Increased	48/214 (22.4%)
Glucose Urine Present	28/214 (13.1%)
Glycosylated Haemoglobin Increased	12/214 (5.6%)
Haematocrit Decreased	12/214 (5.6%)
Haemoglobin Decreased	14/214 (6.5%)
Protein Urine Present	31/214 (14.5%)
Red Blood Cell Count Decreased	11/214 (5.1%)
White Blood Cell Count Increased	11/214 (5.1%)
Musculoskeletal and connective tissue disorders
Back Pain	17/214 (7.9%)
Myalgia	11/214 (5.1%)
Nervous system disorders
Dizziness	19/214 (8.9%)
Headache	11/214 (5.1%)
Psychiatric disorders
Insomnia	12/214 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	13/214 (6.1%)
Upper Respiratory Tract Inflammation	14/214 (6.5%)
Skin and subcutaneous tissue disorders
Rash	18/214 (8.4%)

Limitations/Caveats

Because there was no placebo arm the net effect of rosuvastatin was not clarified. This study examined only single measurable plaques, which might not represent pan-coronary nature of plaque.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.