title: Inhibiting the progression of arterial calcification with vitamin K in HemoDialysis patients (iPACK-HD) trial: rationale and study design for a randomized trial of vitamin K in patients with end stage kidney disease.
abstract: BACKGROUND
  Cardiovascular disease, which is due in part to progressive vascular calcification, is the leading cause of death among patients with end stage kidney disease (ESKD) on dialysis. A role for vitamin K in the prevention of vascular calcification is plausible based on the presence of vitamin K dependent proteins in vascular tissue, including matrix gla protein (MGP). Evidence from animal models and observational studies support a role for vitamin K in the prevention of vascular calcification. A large-scale study is needed to investigate the effect of vitamin K supplementation on the progression of vascular calcification in patients with ESKD, a group at risk for sub-clinical vitamin K deficiency.
  
  
  METHODS
  We plan a prospective, randomized, double-blind, multicenter controlled trial of incident ESKD patients on hemodialysis in centers within North America. Eligible subjects with a baseline coronary artery calcium score of greater than or equal to 30 Agatston Units, will be randomly assigned to either the treatment group (10 mg of phylloquinone three times per week) or to the control group (placebo administration three times per week). The primary endpoint is the progression of coronary artery calcification defined as a greater than 15% increase in CAC score over baseline after 12 months.
  
  
  CONCLUSIONS
  Vitamin K supplementation is a simple, safe and cost-effective nutritional strategy that can easily be integrated into patient care. If vitamin K reduces the progression of coronary artery calcification it may lead to decreased morbidity and mortality in men and women with ESKD.
  
  
  BACKGROUND
  NCT 01528800.
authors.affiliation: Department of Medicine, Queen's University, 3048C Etherington Hall, Kingston, Ontario K7L 3 V6 Canada ; Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario Canada.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Holden
authors.affiliation: USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.affiliation: Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario Canada.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Day
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario Canada.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clase
authors.affiliation: Department of Nephrology, University of Ottawa, Ottawa, Ontario Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Zimmerman
authors.affiliation: Department of Medicine, Western University, London, Ontario Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Moist
authors.affiliation: USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA USA.
authors.forename: M Kyla
authors.initials: MK
authors.lastname: Shea
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario Canada.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: McCabe
authors.affiliation: Women's College Research Institute and Department of Endocrinology, University of Toronto, Toronto, Ontario Canada.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Jamal
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario Canada.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Tobe
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Weinstein
authors.affiliation: Department of Medicine, Tufts University, Boston, MA USA.
authors.forename: Rao
authors.initials: R
authors.lastname: Madhumathi
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Adams
authors.affiliation: Department of Medicine, Queen's University, 3048C Etherington Hall, Kingston, Ontario K7L 3 V6 Canada ; Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario Canada.
authors.forename: Daren K
authors.initials: DK
authors.lastname: Heyland
keywords: Coronary artery calcification; End stage kidney disease; Hemodialysis; Randomized controlled trial; Vitamin K