Study of Asian Patients With Hypercholesterolaemia in the UK - Rosuvastatin 5mg Versus Atorvastatin 10mg

• Sponsor: AstraZeneca (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00427960
• Collaborator: (none)
• Enrollment: 55
• Locations: 9
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness and safety of rosuvastatin 5mg in lowering blood cholesterol, compared to one other medicine, atorvastatin 10mg in Asian patients in the UK.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolaemia	Behavioral: Dietary advice; Drug: rosuvastatin; Drug: atorvastatin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Phase IV, 6-week, Randomised, Double-blind, Multicentre, Parallel Group, Comparative Study to Evaluate the Efficacy of Rosuvastatin 5mg and Atorvastatin 10mg in UK Asian Subjects With Primary Hypercholesterolaemia
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: rosuvastatin rosuvastatin 5 mg	Behavioral: Dietary advice; Drug: rosuvastatin; rosuvastatin 5 mg; Other Names: Crestor
Active Comparator: atorvastatin atorvastatin 10 mg	Behavioral: Dietary advice; Drug: atorvastatin; atorvastatin 10 mg

Outcome Measures

Primary Outcome Measures

1. Percentage Change in Low Density Lipoprotein - Cholesterol (LDL-C) [6 weeks (baseline) and 12 weeks]

   Calculated as LDL-C at Week 6 - LDL-C at Week 12] * 100

Secondary Outcome Measures

1. The Percentage of Participants Reaching the General Medical Services (GMS) Contract Target of Total Cholesterol (TC) <5 mmol/L [6 weeks (Baseline) and 12 weeks]

2. The Percentage of Participants Reaching the Joint British Societies' Guideline (JBS 2) Targets of TC <4 mmol/L and LDL-C <2 mmol/L [6 weeks (baseline) and 12 weeks]

3. The Percentage of Participants Reaching the European (EAS) Targets of LDL-C<2.5 or 3.00 mmol/L, Depending on Risk Category, and the Combined LDL-C and TC Target of LDL-C<2.5 or 3.0 mmol/L and TC<4.5 or 5.0 mmol/L, Both Depending on Risk Category. [6 weeks (baseline) and 12 weeks]

   Risk categories are: Symptomatic Asymptomatic, total risk <5% Asymptomatic, total risk ≥5%, baseline LDL-C<3 mmol/L and baseline TC<5 mmol/L Asymptomatic, total risk ≥5%, baseline LDL-C ≥3 mmol/L or baseline TC ≥5 mmol/L Patients are defined as symptomatic if they meet at least 1 of the following criteria: History of cardiovascular disease Type II diabetes or diabetes of unknown type Baseline TC ≥8 mmol/l Baseline LDL-C ≥6 mmol/l Baseline systolic BP ≥180 mmHg Baseline diastolic BP ≥110 mmHg Total risk is derived from age, sex, TC, systolic BP and smoking status.

4. The Percentage Change From Baseline(week6) in TC [6 weeks (baseline) and 12 weeks]

   Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

5. The Percentage Change From Baseline (Week 6) in High-density Lipoprotein Cholesterol (HDL-C) [6 weeks (baseline) and 12 weeks]

   Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

6. The Percentage of Participants Reaching the Joint British Societies Guideline (JBS 2) Target of TC <4 mmol/L [6 weeks (baseline) and 12 weeks]

7. The Percentage Change From Baseline (Week 6)in Non-HDL-C [6 weeks (baseline) and 12 weeks]

   Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

8. The Percentage Change From Baseline (Week 6) in Apolipoprotein-B (ApoB) [6 weeks (baseline) and 12 weeks]

   Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

9. The Percentage Change From Baseline (Week 6) in Apolipoprotein-A1 (ApoA1) [6 weeks (baseline) and 12 weeks]

   Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

10. The Percentage Change From Baseline (Week 6)in LDL-C/HDL-C Ratio [6 weeks (baseline) and 12 weeks]

    Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

11. The Percentage Change From Baseline (Week 6) in TC/HDL-C Ratio [6 weeks (baseline) and 12 weeks]

    Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

12. The Percentage Change From Baseline(Week 6) in Non-HDL-C/HDL-C Ratio [6 weeks (baseline) and 12 weeks]

    Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

13. The Percentage Change From Baseline (Week 6) in ApoB/ApoA1 Ratio [6 weeks (baseline) and 12 weeks]

    Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6

14. The Percentage of Participants Reaching the European (EAS) Targets of LDL-C<2.5 or 3.00 mmol/L, Depending on Risk Category. [6 weeks (baseline) and 12 weeks]

    Risk categories are: Symptomatic Asymptomatic, total risk <5% Asymptomatic, total risk ≥5%, baseline LDL-C<3 mmol/L and baseline TC<5 mmol/L Asymptomatic, total risk ≥5%, baseline LDL-C ≥3 mmol/L or baseline TC ≥5 mmol/L Patients are defined as symptomatic if they meet at least 1 of the following criteria: History of cardiovascular disease Type II diabetes or diabetes of unknown type Baseline TC ≥8 mmol/l Baseline LDL-C ≥6 mmol/l Baseline systolic BP ≥180 mmHg Baseline diastolic BP ≥110 mmHg Total risk is derived from age, sex, TC, systolic BP and smoking status.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Self described Asian, first or second generation

• Male or female > or = 18 years with primary hypercholesterolaemia.

Exclusion Criteria:

• Use of cholesterol lowering drugs from visit 1

• Homozygous familial hypercholesterolaemia

• Active arterial disease within 3 months of study entry

• Poorly controlled diabetes

• Uncontrolled hypothyroidism

• Active liver disease

• History of alcoh/drug abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Allerton		United Kingdom
2	Research Site	Birmingham		United Kingdom
3	Research Site	Blackburn		United Kingdom
4	Research Site	Bolton		United Kingdom
5	Research Site	Crawley		United Kingdom
6	Research SIte	Glasgow		United Kingdom
7	Research Site	Newcastle		United Kingdom
8	Research SIte	Sheffield		United Kingdom
9	Research SIte	Slough		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Rhiannon Rowsell, MD, AstraZeneca
• Principal Investigator: Shahid Ali, MD, Bradford PCT

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00427960
• Other Study ID Numbers: D3560L00060; SHUKRA
• First Posted: Jan 29, 2007
• Last Update Posted: Dec 16, 2010
• Last Verified: Nov 1, 2010

• Keywords provided by , ,: cholesterol; statin; Asian; LDL-cholesterol
• Additional relevant MeSH terms: Hypercholesterolemia; Atorvastatin; Rosuvastatin Calcium

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 25 primary and secondary care centres in the United Kingdom. The first participant was enrolled on 20th December 2006 and the last participant entered the study on 16th November 2007.
Pre-assignment Detail	Participants entered an initial 6-week dietary run-in/ wash-out period, after which those with a fasting low density lipoprotein cholesterol (LDL-C) of greater than or equal to 4.00 mmol/L and triglycerides (TG) less than 4.52 mmol/L, were randomised to receive treatment with either rosuvastatin 5 mg plus atorvatstatin , or atorvastatin 10mg

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Period Title: Overall Study
STARTED	30	25
COMPLETED	28	21
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Rosuvastatin	Atorvastatin	Total
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg	Total of all reporting groups
Overall Participants	30	25	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (11)	53 (11)	51.5 (11)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	11 44%	24.0 43.6%
Male	17 56.7%	14 56%	31.0 56.4%

Outcome Measures

1. Primary Outcome

Title	Percentage Change in Low Density Lipoprotein - Cholesterol (LDL-C)
Description	Calculated as LDL-C at Week 6 - LDL-C at Week 12] * 100
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in LDL-C]	33.28	36.92

2. Secondary Outcome

Title	The Percentage of Participants Reaching the General Medical Services (GMS) Contract Target of Total Cholesterol (TC) <5 mmol/L
Time Frame	6 weeks (Baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percentage of Participants]	50 166.7%	64 256%

3. Secondary Outcome

Title	The Percentage of Participants Reaching the Joint British Societies' Guideline (JBS 2) Targets of TC <4 mmol/L and LDL-C <2 mmol/L
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percentage of Participants]	16 53.3%	28 112%

4. Secondary Outcome

Title	The Percentage of Participants Reaching the European (EAS) Targets of LDL-C<2.5 or 3.00 mmol/L, Depending on Risk Category, and the Combined LDL-C and TC Target of LDL-C<2.5 or 3.0 mmol/L and TC<4.5 or 5.0 mmol/L, Both Depending on Risk Category.
Description	Risk categories are: Symptomatic Asymptomatic, total risk <5% Asymptomatic, total risk ≥5%, baseline LDL-C<3 mmol/L and baseline TC<5 mmol/L Asymptomatic, total risk ≥5%, baseline LDL-C ≥3 mmol/L or baseline TC ≥5 mmol/L Patients are defined as symptomatic if they meet at least 1 of the following criteria: History of cardiovascular disease Type II diabetes or diabetes of unknown type Baseline TC ≥8 mmol/l Baseline LDL-C ≥6 mmol/l Baseline systolic BP ≥180 mmHg Baseline diastolic BP ≥110 mmHg Total risk is derived from age, sex, TC, systolic BP and smoking status.
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percentage of Participants]	43 143.3%	48 192%

5. Secondary Outcome

Title	The Percentage Change From Baseline(week6) in TC
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in TC]	-23.03	-26.88

6. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6) in High-density Lipoprotein Cholesterol (HDL-C)
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in HDL-C]	4.46	3.15

7. Secondary Outcome

Title	The Percentage of Participants Reaching the Joint British Societies Guideline (JBS 2) Target of TC <4 mmol/L
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percentage of Participants]	13 43.3%	12 48%

8. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6)in Non-HDL-C
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in Non-HDL-C]	-29.72	-34.09

9. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6) in Apolipoprotein-B (ApoB)
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in ApoB]	-25.96	-28.67

10. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6) in Apolipoprotein-A1 (ApoA1)
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in ApoA1]	-0.55	1.89

11. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6)in LDL-C/HDL-C Ratio
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in LDL-C/HDL-C Ratio]	-34.75	-38.45

12. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6) in TC/HDL-C Ratio
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in TC/HDL-C Ratio]	-24.99	-28.42

13. Secondary Outcome

Title	The Percentage Change From Baseline(Week 6) in Non-HDL-C/HDL-C Ratio
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in Non-HDL-C/HDL-C Ratio]	-31.05	-35.48

14. Secondary Outcome

Title	The Percentage Change From Baseline (Week 6) in ApoB/ApoA1 Ratio
Description	Derived according to the following formula: 100*[Lipid at week 12 - Lipid at week 6]/Lipid at week 6
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percent Change in ApoB/ApoA1 Ratio]	-22.89	-28.75

15. Secondary Outcome

Title	The Percentage of Participants Reaching the European (EAS) Targets of LDL-C<2.5 or 3.00 mmol/L, Depending on Risk Category.
Description	Risk categories are: Symptomatic Asymptomatic, total risk <5% Asymptomatic, total risk ≥5%, baseline LDL-C<3 mmol/L and baseline TC<5 mmol/L Asymptomatic, total risk ≥5%, baseline LDL-C ≥3 mmol/L or baseline TC ≥5 mmol/L Patients are defined as symptomatic if they meet at least 1 of the following criteria: History of cardiovascular disease Type II diabetes or diabetes of unknown type Baseline TC ≥8 mmol/l Baseline LDL-C ≥6 mmol/l Baseline systolic BP ≥180 mmHg Baseline diastolic BP ≥110 mmHg Total risk is derived from age, sex, TC, systolic BP and smoking status.
Time Frame	6 weeks (baseline) and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population (all randomized patients).

Arm/Group Title	Rosuvastatin	Atorvastatin
Arm/Group Description	rosuvastatin 5 mg	atorvastatin 10 mg
Measure Participants	30	25
Number [Percentage of Participants]	56.7 189%	56.0 224%

Adverse Events

Arm/Group Title	Rosuvastatin		Atorvastatin
Arm/Group Description	rosuvastatin 5 mg		atorvastatin 10 mg
All Cause Mortality
	Rosuvastatin		Atorvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rosuvastatin		Atorvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		0/ (NaN)
Nervous system disorders
Cerebrovascular Accident	1/30 (3.3%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Rosuvastatin		Atorvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/ (NaN)		3/ (NaN)
Nervous system disorders
Dizziness	3/30 (10%)		1/25 (4%)
Headache	1/30 (3.3%)		2/25 (8%)

Limitations/Caveats

The study achieved only 8% of the randomised target number of patients and for this reason alone was terminated early. Planned statistical analyses could not be performed. No scientifically valid conclusions can be drawn from the limited study data.

More Information

Certain Agreements

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