Condition category
Circulatory System
Date applied
13/09/2008
Date assigned
17/09/2008
Last edited
17/09/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ascan Warnholtz

ORCID ID

Contact details

Johannes Gutenberg-Universität Mainz
Department of Medicine II
Langenbeckstrasse 1
Mainz
D-55131
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

CEZAR

Study hypothesis

Atorvastatin 80 mg per day is more effective in the improvement of flow-mediated dilation of the right brachial artery than atorvastatin 10 mg plus ezetimibe 10 mg per day despite comparable reduction of plasma low-density lipoprotein (LDL) cholesterol concentration.

Ethics approval

1. Ethics Committee of the Medical Association of Hamburg (Ethik-Kommission der Ärztekammer Hamburg), approved on 13/03/2003
2. State Medical Board of Registration in Rhineland-Palatinate (Landesärztekammer Rhineland-Palatinate), approved on 07/11/2005

Study design

Phase IV, double-blind, two-arm, parallel-group, randomised controlled trial (single-centre)

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Stable coronary artery disease

Intervention

Arm 1: Atorvastatin (oral) 80 mg per day for 8 weeks
Arm 2: Atorvastatin (oral) 10 mg + ezetimibe (oral) 10 mg per day for 8 weeks

Ultrasonic measurements of endothelial function were carried out at the beginning of treatment and at the end of the 8-week pharmacological intervention.

Intervention type

Drug

Phase

Not Specified

Drug names

Ezetimibe and atorvastatin

Primary outcome measures

Effect of treatment on the absolute change (in percentage) in flow-mediated dilation (FMD) at 8 weeks compared to baseline.

Secondary outcome measures

Effect of treatment, at 8 weeks compared to baseline, on the following:
1. Absolute change (in percentage) in nitroglycerin-mediated dilation (NMD)
2. Absolute change in LDL cholesterol plasma concentration
3. Absolute change in C-reactive protein plasma concentration
4. Absolute change in uric acid plasma concentration
5. Absolute change in 8-iso-prostaglandin F2 alpha urine concentration

Overall trial start date

01/07/2003

Overall trial end date

31/07/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Both males and females, over 18 years old
2. Angiographic, documented coronary heart disease with:
a. Generalized wall irregularities (stenosis <40%) and/or
b. Existence of at least one stenosis >50%
3. Endothelial dysfunction with flow-dependent dilation of the brachial artery of <6%
4. LDL cholesterol >100 mg/dl
5. Written consent of the patients for participation in the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

58

Participant exclusion criteria

1. Acute coronary syndrome
2. Stroke or peripheral revascularisation within 12 weeks before study enrolment
3. Known intolerance towards HMG CoA reductase inhibitors or ezetimibe
4. Clinically significant valvular disease
5. Hypertrophic obstructive cardiomyopathy
6. Sustained ventricular arrhythmias
7. Syncope within four weeks before the study
8. Severe respiratory disease
9. Unstable diabetes mellitus requiring frequent adjustments in insulin doses
10. Known hypothyroidism
11. Known hyperthyroidism
12. Gastrointestinal disorders (such as Crohn's disease), which could lead to decreased absorption of the study drug
13. Chronic liver disease
14. History of pancreatitis
15. History of organ transplantation
16. Clinically significant heart failure with left ventricular ejection fraction of <30%
17. Symptoms of orthostatic hypotension, or a systolic blood pressure in the supine position of <90 mmHg
18. Systolic blood pressure >180 mmHg and/or diastolic blood pressure >105 mmHg despite antihypertensive therapy
19. Elevated serum creatinine of >2.0 mg/dL or known nephrotic syndrome
20. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 times above the upper normal limit
21. Triglyceride level >400 mg/dl
22. Treatment with an HMG CoA reductase inhibitor during the last three months
23. Treatment with ezetimibe during the last three months
24. Initiation of treatment with an angiotensin converting enzyme (ACE) inhibitor, AT1-receptor antagonist, or calcium channel blocker within the past four weeks
25. Treatment with fibrates or colestipol during the last three months
26. Current treatment with macrolide antibiotics, niacin or antimycotics of azole type
27. Expected problems with compliance or follow-up visits (no fixed residence, alcohol or drug abuse, history of failure of medical advice, psychiatric diseases, etc.)
28. For women: pregnancy, breast feeding or possible pregnancy (women of childbearing age on an acceptable method of contraception may be included)
29. Simultaneous participation in another study
30. Therapy with another investigational product within a period of 30 days before the study

Recruitment start date

01/07/2003

Recruitment end date

31/07/2006

Locations

Countries of recruitment

Germany

Trial participating centre

Johannes Gutenberg-Universität Mainz
Mainz
D-55131
Germany

Sponsor information

Organisation

Johannes Gutenberg-University Mainz (Germany)

Sponsor details

c/o Prof. Dr. T. Münzel
Department of Medicine II
Langenbeckstrasse 1
Mainz
D-55101
Germany

Sponsor type

University/education

Website

http://www.uni-mainz.de/eng

Funders

Funder type

University/education

Funder name

University of Hamburg (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Johannes Gutenberg-University Mainz (Germany)

Alternative name(s)

Johannes Gutenberg University Mainz, JGU

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Germany

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes