June 16, 2008 |
June 17, 2008 |
June 2008 |
The degree of inflammation in stenotic aortic valves [ Time Frame: 3-5 months ] [ Designated as safety issue: No ] |
Same as current |
Complete list of historical versions of study NCT00699452 on ClinicalTrials.gov Archive Site |
The degree of calcification, lipid accumulation, and fibrosis in stenotic aortic valves [ Time Frame: 3-5 months ] [ Designated as safety issue: No ] |
Same as current |
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The Potential of Rosuvastatin and Candesartan to Retard the Progression of Aortic Stenosis |
The Potential of Rosuvastatin and Candesartan to Retard the Progression of Aortic Stenosis Influences of Medical Therapy to the Atheroinflammatory Process in Stenotic Aortic Valves |
The present study defines a blinded, randomized, placebo-controlled, prospective study, the aim of which is to determine the influence of intensive statin therapy, using rosuvastatin (target dose 20 mg), and effective treatment with AT-1R antagonist, using candesartan (target dose 16 mg) on stenotic aortic valves. We will specifically quantify whether these drugs attenuate the key pathogenic mechanisms of aortic valve stenosis, namely inflammation, fibrosis, elastin degradation, calcification, and neovascularization. |
We will include in the study 120 consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery.Patients who can be put on the hospital's normal waiting list for elective angiography (i.e who do not need urgent surgery) and who give their informed consent, will be randomized into four groups to start therapy with rosuvastatin (10 mg/d for 2 weeks, and then 20 mg/d until surgery) or candesartan (8 mg/d for 2 weeks, and then 16 mg/d until surgery), a combined rosuvastatin and candesartan therapy, or placebo. On average, the overall duration of the drug intervention will be 3 months, i.e. the average time in our institution from referral to surgery. In addition, patients (n=50) undergoing aortic valve replacement surgery due to aortic regurgitation caused by dilation of the aortic root will be included. This population consists of both patients with early sclerotic, i.e. pre-stenotic, changes in their aortic valves (n=30) and of patients without any sclerotic or stenotic changes in their aortic valves (n=20). The group with sclerotic changes in their aortic valves (n=30) will be divided into two groups to receive both rosuvastatin (10 mg/d fro 2 wk and thereafter 20 mg/d until surgery) and candesartan (8 mg/d 2 wk, and then 16 mg/d until surgery) (n=15), or placebo + placebo (n=15).The removed aortic valves will be examined utilizing real-time PCR, autoradiography, fluorometry, immunohistochemistry, double immunofluorecence, confocal microscopy, and enzyme immunoassays. With these techniques, several markers of inflammation, calcification, fibrosis, and the amount of lipid accumulation and oxidation of LDL in the valves will be examined. |
Phase III |
Interventional |
Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Aortic Valve Stenosis |
- Drug: rosuvastatin
- Drug: candesartan
- Drug: rosuvastatin and candesartan
- Drug: placebo
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- Active Comparator: Rosuvastatin 10 mg/d for 2 weeks, then 20 mg/d until surgery (approximately 3 months)
- Active Comparator: Candesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months)
- Active Comparator: Combination therapy: Rosuvastatin 10 mg/d for 2 weeks, then 20 mg/d and candesartan 8 mg/d for two weeks, then 16 mg/d until valve replacement surgery (approximately 3 months)
- Placebo Comparator: Placebo
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Recruiting |
120 |
December 2013 |
December 2011 (final data collection date for primary outcome measure) |
Inclusion Criteria:
- 120 consecutive patients with clinically significant, symptomatic aortic stenosis referred to the Helsinki University Central Hospital for consideration of valve replacement surgery.
Exclusion Criteria:
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Both |
18 Years and older |
No |
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Finland |
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NCT00699452 |
Markku Kupari, Division of Cardiology, Helsinki University Central Hospital |
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Helsinki University |
AstraZeneca |
Principal Investigator: |
Markku Kupari, MD, PhD |
Division of Cardiology, Helsinki University Central Hospital |
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Helsinki University |
June 2008 |