Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial

Jes Sanddal Lindholt, Niels Erik Frandsen, Maise Høigaard Fredgart, Kristian A Øvrehus, Jordi Sanchez Dahl, Jacob Eifer Møller, Lars Folkestad, Grazina Urbonaviciene, Søren Warberg Becker, Jess Lambrechtsen, Søren Auscher, Susanne Hosbond, Dilek Hunerel Alan, Lars Melholt Rasmussen, Oke Gerke, Hans Mickley, Axel Diederichsen, Jes Sanddal Lindholt, Niels Erik Frandsen, Maise Høigaard Fredgart, Kristian A Øvrehus, Jordi Sanchez Dahl, Jacob Eifer Møller, Lars Folkestad, Grazina Urbonaviciene, Søren Warberg Becker, Jess Lambrechtsen, Søren Auscher, Susanne Hosbond, Dilek Hunerel Alan, Lars Melholt Rasmussen, Oke Gerke, Hans Mickley, Axel Diederichsen

Abstract

Introduction: 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). We hypothesise that MK-7 supplementation will slow down the calcification process.

Methods and analysis: In this multicenter and double-blinded, placebo-controlled study, 400 men aged 65-74 years with substantial AVC are randomised (1:1) to treatment with MK-7 (720 µg/day) supplemented by the recommended daily dose of vitamin D (25 µg/day) or placebo treatment (no active treatment) for 2 years. Exclusion criteria are treatment with vitamin K antagonist or coagulation disorders. To evaluate AVC score, a non-contrast CT scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is difference in AVC score from baseline to follow-up at 2 years. Intention-to-treat principle is used for all analyses.

Ethics and dissemination: There are no reported adverse effects associated with the use of MK-7. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010). It is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported.

Trial registration number: NCT03243890.

Keywords: aortic valve calcification; cardiovascular imaging; menaquinone-7; randomized clinical trial; valvular heart disease.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Timeline and applied tests (for details please see the Applied tests during the study section).

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