title: Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol.
abstract: BACKGROUND
  Patients on haemodialysis (HD) exhibit increased cardiovascular mortality associated with accelerated vascular calcification (VC). VC is influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and supplementation with vitamin K reduces inactive MGP levels in these patients. The VitaVasK trial analyses whether vitamin K1 supplementation affects the progression of coronary and aortic calcification in HD patients.
  
  
  METHODS
  VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score of at least 100 will be randomized to continue on standard care or to receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes in the volume scores at the 18-month MSCT versus the baseline MSCT). Secondary end points comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and all-cause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients.
authors.affiliation: Department of Nephrology and Immunology, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Krueger
authors.affiliation: Department of Nephrology and Immunology, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schlieper
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands.
authors.forename: Leon
authors.initials: L
authors.lastname: Schurgers
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Cornelis
authors.affiliation: Renal Division, University of Milan, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Jacobi
authors.affiliation: Division of Nephrology, Cliniques universitaires Saint-Luc Université catholique de Louvain, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Jadoul
authors.affiliation: Department of Nephrology, Klinikum Coburg, Coburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
authors.affiliation: Department of Nephrology, University Hospital of Duesseldorf, Germany.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Rump
authors.affiliation: Department of Renal Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.affiliation: Department of Cardiology, University Hospital of Duesseldorf, Duesseldorf, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Westenfeld
authors.affiliation: Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiecek
authors.affiliation: Department of Radiology, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reinartz
authors.affiliation: Institute of Medical Statistics, RWTH University Aachen, Aachen, Germany.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hilgers
authors.affiliation: Department of Nephrology and Immunology, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000502:physiology; D003324:Coronary Artery Disease / Q000188:drug therapy; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D015337:Multicenter Studies as Topic; D018579:Patient Selection; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D014057:Tomography, X-Ray Computed; D061205:Vascular Calcification / Q000503:physiopathology / Q000517:prevention & control*; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000627:therapeutic use*; D000097568:Matrix Gla Protein
chemical_list: D000933:Antifibrinolytic Agents; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D010837:Vitamin K 1; D000097568:Matrix Gla Protein
keywords: haemodialysis; matrix Gla protein; vascular calcification; vitamin K