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Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial
  1. Jes Sanddal Lindholt1,2,
  2. Niels Erik Frandsen3,
  3. Maise Høigaard Fredgart4,
  4. Kristian A Øvrehus4,
  5. Jordi Sanchez Dahl4,
  6. Jacob Eifer Møller4,
  7. Lars Folkestad5,
  8. Grazina Urbonaviciene6,
  9. Søren Warberg Becker6,
  10. Jess Lambrechtsen7,
  11. Søren Auscher7,
  12. Susanne Hosbond8,
  13. Dilek Hunerel Alan8,
  14. Lars Melholt Rasmussen2,9,
  15. Oke Gerke10,
  16. Hans Mickley4,
  17. Axel Diederichsen2,4
  1. 1 Department of Cardiothoracic and Vascular Surgery, Odense Universitetshospital, Odense, Denmark
  2. 2 Centre for Individualized Medicine in Arterial Diseases, Odense Universitetshospital, Odense, Denmark
  3. 3 Kirkestenten 16, Skt Klemens, Odense C, Denmark
  4. 4 Department of Cardiology, Odense Universitetshospital, Odense, Denmark
  5. 5 Department of Endocrinology, Odense Universitetshospital, Odense, Denmark
  6. 6 Department of Cardiology, Silkeborg Hospital, Silkeborg, Denmark
  7. 7 Department of Cardiology, Svendborg Sygehus, Svendborg, Syddanmark, Denmark
  8. 8 Department of Cardiology, Vejle Hospital, Vejle, Denmark
  9. 9 Department of Clinical Biochemistry and Pharmacology, Odense Universitetshospital, Odense, Denmark
  10. 10 Department of Nuclear Medicine, Odense Universitetshospital, Odense C, Denmark
  1. Correspondence to Dr Axel Diederichsen; axel.diederichsen{at}rsyd.dk

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.

  • menaquinone-7
  • aortic valve calcification
  • valvular heart disease
  • cardiovascular imaging
  • randomized clinical trial

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors JSL, NEF, LMR and AD conceived and designed the study. AD wrote the study protocol and is the principal investigator while JSL, NEF and LMR are coinvestigators. MHF is the clinical research fellow responsible for the running of the clinical trial. KAØ is responsible for the Cardiac-CT contrast protocol. JSD and JEM are responsible for the echocardiography protocol. GU (Silkeborg), SWB (Silkeborg), JL (Svendborg), SA (Svendborg), SH (Vejle) and DHA (Vejle) are site-specific coinvestigators. LF is involved in the bone-related substudy. OG is responsible for statistics. HM is representative for the DSMB. All authors have contributed to the revision of the manuscript.

  • Funding The trial is supported by the Danish Heart Foundation (grant number 17-R116-A7569-22071), Region of Southern Denmark’s Research council (grant number 17/15638) and the Novo Nordisk Foundation (grant number NNF17OC0029076). The study tablets, including placebo, are provided for free of charge by Kappa Bioscience A/S, Silurveien 2B, 0380 Oslo and Orkla Care, Industrigrenen 10, 2635 Ishøj. The companies are not involved in the execution of the study or analysis of the data.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Positive as well as negative findings will be reported via conference presentations and peer-reviewed publications. All the data will be available upon request.

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