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.

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.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / diagnostic imaging
  • Aortic Valve Stenosis / drug therapy*
  • Calcinosis / diagnostic imaging
  • Calcinosis / drug therapy*
  • Disease Progression
  • Hemostatics / therapeutic use*
  • Humans
  • Male
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Tomography, X-Ray Computed
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / therapeutic use

Substances

  • Hemostatics
  • Vitamin K 2
  • menaquinone 7

Supplementary concepts

  • Aortic Valve, Calcification of

Associated data

  • ClinicalTrials.gov/NCT03243890