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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | Study drug. Supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day) |
|
| Placebo | Placebo Comparator | Placebo tablet (no active treatment). The placebo tablet is matched to the study drug for taste, color, and size. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day). | Dietary Supplement | 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). |
| 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 |
| 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 |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Axel CP Diederichsen, PhD | Odense University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiology, Odense University Hospital | Odense | Odense C | DK-5000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30139903 | Background | Lindholt JS, Frandsen NE, Fredgart MH, Ovrehus KA, Dahl JS, Moller JE, Folkestad L, Urbonaviciene G, Becker SW, Lambrechtsen J, Auscher S, Hosbond S, Alan DH, Rasmussen LM, Gerke O, Mickley H, Diederichsen A. Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial. BMJ Open. 2018 Aug 23;8(8):e022019. doi: 10.1136/bmjopen-2018-022019. | |
| 35465686 |
| Label | URL |
|---|---|
| Protocol | View source |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 24, 2021 | Jul 29, 2021 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C062629 | menaquinone 7 |
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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.
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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.
| Placebo | Dietary Supplement | Half of the patients are randomized to placebo treatment (no active treatment). |
|
| 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 |
| Derived |
| Diederichsen ACP, Lindholt JS, Moller S, Ovrehus KA, Auscher S, Lambrechtsen J, Hosbond SE, Alan DH, Urbonaviciene G, Becker SW, Fredgart MH, Hasific S, Folkestad L, Gerke O, Rasmussen LM, Moller JE, Mickley H, Dahl JS. Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation. 2022 May 3;145(18):1387-1397. doi: 10.1161/CIRCULATIONAHA.121.057008. Epub 2022 Apr 25. |
| D014694 |
| Ventricular Outflow Obstruction |