Vitamin K to Attenuate Coronary Artery Calcification in Hemodialysis Patients (iPACK HD)

• Feasibility of recruiting pts to trial [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• compliance with study intervention over 6 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• drop-out rate of study patients [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• adherence to study protocol [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• pilot electronic data capture system [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• determine logistics of future multi-center trial [ Time Frame: 12 months ] [ Designated as safety issue: No ]

• biomarkers of vitamin K [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
• cardiovascular events [ Time Frame: monthly assessed ] [ Designated as safety issue: No ]
• mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• coronary artery calcification [ Time Frame: 12 months ] [ Designated as safety issue: No ]

• biomarkers of vitamin K [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
• cadiovascular events [ Time Frame: monthly assessed ] [ Designated as safety issue: No ]
• mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• coronary artery calcification [ Time Frame: 6 months ] [ Designated as safety issue: No ]

The purpose of this study is to see if vitamin K supplementation three times per week reduces the progression of coronary artery calcification over 12 months in dialysis patients compared to placebo?

At every stage of chronic kidney disease (CKD), the leading cause of mortality is cardiovascular disease. This is due, in part, to vascular calcification of the coronary arteries. The extent of VC in the coronary arteries of patients with CKD is commonly determined by high resolution CT scan. The total coronary artery calcium (CAC) score, measured in Agatston units (AUs), reflects the calcium burden in the 3 major coronary arteries and is the current standard for determining extent of vascular calcification in hemodialysis patients. Matrix Gla protein (MGP), a vitamin K dependent protein, is a key inhibitor of vascular calcification and is present in the arterial wall. It is established that MGP becomes up-regulated adjacent to sites of calcification and that vitamin K is critical to its function. Therefore vitamin K status may be critical to the extent of vascular calcification in this patient group. However, to date, no trial has examined whether vitamin K supplementation prevents the progression of coronary artery calcification in patients with kidney failure, a group in which high risk has been established. Therefore, our primary research question is: Does vitamin K supplementation with 10 mg of phylloquinone thrice weekly reduce the progression of coronary artery calcification (as measured by CAC score) over 12 months in incident hemodialysis patients with a baseline CAC score of >= 30 Agatston Units compared to placebo? Secondary questions include: 1) Does phylloquinone reduce the progression of calcification in the thoracic aorta, aortic valve and mitral valve? and 2) Does phylloquinone decrease major cardiovascular events such as acute coronary syndrome, congestive heart failure, stroke, transient ischemic attack, amputation or revascularization procedure?

• Drug: Vitamin K1
  10mg orally three times a week for 12 months
  Other Name: phytonadione
• Drug: Chrystalline Lactose
  10mg orally three times a week for 12 months

• Placebo Comparator: Placebo
  Chrystalline Lactose
  Intervention: Drug: Chrystalline Lactose
• Active Comparator: Vitamin K1
  Vitamin K1
  Intervention: Drug: Vitamin K1

Inclusion Criteria:

• have end stage kidney disease and are new to hemodialysis (< 6 months)
• >=18 years
• have a baseline coronary artery calcification score >=30AUs
• are expected to survive one year
• are able to provide signed informed consent

Exclusion Criteria:

• have a medical condition that requires warfarin
• require hemodialysis for acute kidney injury
• are pregnant
• have other sever co-morbid conditions (e.g. malignancy, disabling stroke) with life expectancy less than one year
• have undergone coronary artery bypass grafting or have stents placed in their coronary arteries
• are currently enrolled in another interventional trial