Aortic Valve Stenosis, Multidetector Computed Tomography, Randomised Clinical Trial, Vitamin K 2
Conditions
Brief summary
Aortic stenosis is a common heart valve disease and due to the growing elderly population the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed, thus presently the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). The investigators hypothesize that MK-7 supplementation will slow down the calcification process.
Interventions
DIETARY_SUPPLEMENTMenaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).
Half of the patients are randomized to supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day).
DIETARY_SUPPLEMENTPlacebo
Half of the patients are randomized to placebo treatment (no active treatment).
Sponsors
Axel Diederichsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The randomization-list is available to the data and safety monitoring board, but patients, nurses, physicians and other data collectors are kept blinded to the allocation during the study.
Intervention model description
Subjects will be randomized 1:1 after stratification for site, AVC score (300-599 or ≥600) and statin-use. Each site will be provided with sequentially numbered, opaque and sealed envelopes containing randomly generated treatment allocations. Four different types of envelopes are provided; 1) AVC 300-599, no statin-use; 2) AVC 300-599, statin-use; 3) AVC ≥600, no statin-use; and 4) AVC ≥600, statin-use.
Eligibility
Sex/Gender
MALE
Age
65 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Participants in the Danish Cardiovascular Screening Trial (Trials. 2015 Dec 5;16:554) with an aortic valve calcification score above 300, but without aortic valve stenosis are eligible.
Exclusion criteria
* Known aortic valve disease (peak velocity ≥3.0 m/s) * History of venous thrombosis or other coagulation disorders or use of vitamin K antagonists * Disorders of calcium and phosphate metabolism * A life-expectancy \< 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aortic valve calcification | From baseline to two years of follow-up | The primary endpoint is the change in aortic valve calcification. The natural history of the aortic valve calcification is not adequately understood, and accordingly the changes are analyzed in two prespecified patient subgroups (AVC score 300-599 and ≥600, respectively). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aortic size | From baseline to two years of follow-up | Change in aortic diameter |
| Coronary plaque composition | From baseline to two years of follow-up | Change in total plaque burden in the coronaries and carotid arteries by contrast CT |
| Aortic valve area | From baseline to two years of follow-up | Change in aortic valve area by transthoracic echocardiography |
| Arterial calcification | From baseline to two years of follow-up | Change in compiled arterial calcification by non-contrast CT |
| Biomarkers of calcification | From baseline to two years of follow-up | Change in matrix-Gla proteins and osteocalcin with different phosphorylation (p and dp) and carboxylation forms (c and uc). |
| Quality of life | From baseline to two years of follow-up | Change in quality of life |
| Bone mineral density | From baseline to two years of follow-up | Change in bone mineral density as quantitative CT of the columna lumbalis and hip region |
Countries
Denmark
Outcome results
None listed