Article Text

Protocol
Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial
  1. Selma Hasific1,
  2. Kristian A Øvrehus1,
  3. Susanne Hosbond2,
  4. Jess Lambrechtsen3,
  5. Preman Kumarathurai1,
  6. Anna Mejldal4,5,
  7. Emil Johannes Ravn1,
  8. Lars Melholt Rasmussen6,7,
  9. Oke Gerke8,
  10. Hans Mickley1,
  11. Axel Diederichsen1
  1. 1Department of Cardiology, Odense University Hospital, Odense, Denmark
  2. 2Department of Cardiology, Sygehus Lillebalt, Vejle, Syddanmark, Denmark
  3. 3Department of Cardiology, Svendborg Hospital, Svendborg, Denmark
  4. 4Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  5. 5Open Patient Data Explorative Network, Odense University, Odense, Denmark
  6. 6Department of Clinical Biochemistry and Pharmacology, Odense Universitetshospital, Odense, Denmark
  7. 7Centre for Individualised Medicine in Arterial Diseases, Odense Universitetshospital, Odense, Denmark
  8. 8Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
  1. Correspondence to Axel Diederichsen; axel.diederichsen{at}rsyd.dk

Abstract

Introduction Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process.

Method and analysis In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses.

Ethics and dissemination There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported.

Trial registration number NCT05500443.

  • Ischaemic heart disease
  • Clinical Trial
  • NUTRITION & DIETETICS
  • PREVENTIVE MEDICINE
  • Cardiovascular imaging
http://creativecommons.org/licenses/by-nc/4.0/

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

  • Twitter @SelmaHasific, @ADiederichsen

  • Contributors Conceptualisation: SH, KAØ and AD; data curation and analysis: SH, AM and AD; funding acquisition: AD; investigation: SH, KAØ, SH, JL, PK, EJR, LMR, OG, HM and AD; project administration: SH and AD; writing—original draft: SH, PK and AD; writing—review and editing: SH, KAØ, SH, JL, PK, AM, EJR, LMR, OG, HM and AD.

  • Funding Private foundations and companies are sought for funding. Study tablets, including placebo, are provided free of charge by Kappa Bioscience, Norway and Orkla Care, Denmark. The companies are not involved in the design, execution of the study, analysis of the data or reporting of results.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.