The Aortic Valve DECalcification (AVADEC) Trial

Study Overview
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Brief Summary
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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.

Official Title
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The Effects of Menaquinone-7 Supplementation in Patients With Aortic Valves Calcification

Conditions
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Aortic Valve Stenosis, Multidetector Computed Tomography, Vitamin K 2, Randomised Clinical Trial

Intervention / Treatment
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* Dietary Supplement: Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Study drug. Supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day) | Dietary Supplement: Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).<br>* 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).<br>|
| Placebo Comparator: Placebo<br>Placebo tablet (no active treatment). The placebo tablet is matched to the study drug for taste, color, and size. | Dietary Supplement: Placebo<br>* Half of the patients are randomized to placebo treatment (no active treatment).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic valve calcification | 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). | From baseline to two years of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial calcification | Change in compiled arterial calcification by non-contrast CT | From baseline to two years of follow-up | 
| Aortic size | Change in aortic diameter | From baseline to two years of follow-up | 
| Coronary plaque composition | Change in total plaque burden in the coronaries and carotid arteries by contrast CT | From baseline to two years of follow-up | 
| Aortic valve area | Change in aortic valve area by transthoracic echocardiography | From baseline to two years of follow-up | 
| Bone mineral density | Change in bone mineral density as quantitative CT of the columna lumbalis and hip region | From baseline to two years of follow-up | 
| Biomarkers of calcification | Change in matrix-Gla proteins and osteocalcin with different phosphorylation (p and dp) and carboxylation forms (c and uc). | From baseline to two years of follow-up | 
| Quality of life | Change in quality of life | From baseline to two years of follow-up |