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 (VC) 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 three 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 prevalent hemodialysis patients with a baseline CAC score of ≥ 30 Agatston Units compared to placebo?
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
85
10mg orally three times a week for 12 months
10mg orally three times a week for 12 months
Kingston Health Sciences Centre: Kingston General Hospital Site
Kingston, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Recruitment rate
Number of participants recruited per month at each site) and an overall crude average of each site's rate.
Time frame: 12 months
Compliance with study medication
Proportion of prescribed doses received.
Time frame: 12 months
Dropout rate
Proportion of participants who dropped out from the trial.
Time frame: 12 months
Adherence to study protocol
Proportion of participants who adhered to the study protocol.
Time frame: 12 months
Rates of eligible patients consented and randomized
Proportion of eligible patients consented and randomized.
Time frame: 12 months
Coronary artery calcification (Agatston calcium scores) progression
A)The percent and absolute change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline. Included measures will be: Total CAC, Left Main CAC, Right Coronary Artery CAC, Left Anterior Descending CAC, Circumflex CAC, and Posterior Descending Artery CAC. B) The proportion of participants with a 15% or greater increase in Agatston calcium scores will be assessed at study exit vs baseline.
Time frame: 12 months
Coronary artery calcification (volume calcium scores) progression
A) The percent and absolute change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline. Included measures will be: Total CAC, Left Main CAC, Right Coronary Artery CAC, Left Anterior Descending CAC, Circumflex CAC, and Posterior Descending Artery CAC. B) The proportion of participants with a 15% or greater increase in volume calcium scores will be assessed at study exit vs baseline.
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Time frame: 12 months
Coronary artery calcification (Agatston calcium scores) regression
The proportion of participants with a 10% or greater decrease in Agatston calcium scores will be assessed at study exit vs baseline.
Time frame: 12 months
Coronary artery calcification (volume calcium scores) regression
The proportion of participants with a 10% or greater decrease in volume calcium scores will be assessed at study exit vs baseline.
Time frame: 12 months
Aortic valve calcification (Agatston calcium scores) progression
The absolute and percentage change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline.
Time frame: 12 months
Aortic valve calcification (volume calcium scores) progression
The absolute and percentage change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline.
Time frame: 12 months
Mitral valve calcification (Agatston calcium scores) progression
The absolute and percentage change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline.
Time frame: 12 months
Mitral valve calcification (volume calcium scores) progression
The absolute and percentage change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline.
Time frame: 12 months
Abdominal aortic calcification (AAC) scores
The AAC score (mean score in L1-L4, mean number of positive segments, mean total severity using lateral lumbar spine radiographs) will be assessed at study exit vs. baseline.
Time frame: 12 months
Levels of biomarkers of vitamin K status
Gas6, PK, MK4, osteocalcin Gla, osteocalcin Glu, osteocalcin Gla to Glu ratio, percent of osteocalcin undercarboxylated, and dpucMGP will be assessed at baseline, four, eight and study exit. Protein induced by vitamin K absence or antagonist II (PIVKA-II) will be assessed at baseline and study exit.
Time frame: 12 months
Prevalence and incidence of thoracic vertebral fractures
The prevalence and incidence of thoracic vertebral fractures (anterior and lateral radiographs) will be assessed at baseline and study exit.
Time frame: 12 months
Prevalence and incidence of lumbar vertebral fractures
The prevalence and incidence of lumbar vertebral fractures (anterior and lateral radiographs) will be assessed at baseline and study exit.
Time frame: 12 months
Presence/absence and total hospitalizations
The presence or absence and total hospitalizations will be assessed across the study duration per patient.
Time frame: 12 months
Presence/absence and total cardiovascular events
The presence or absence and total cardiovascular events (acute coronary syndrome, congestive heart failure, stroke, transient ischemic attack, amputation, and cardiac \[symptom-driven\] \[cerebral or peripheral\] revascularization procedure, or cardiac arrest) will be assessed across the study duration per patient.
Time frame: 12 months
Presence/absence and total thrombotic events
The presence or absence and total thrombotic events (deep vein thrombosis and pulmonary embolism) will be assessed across the study duration per patient.
Time frame: 12 months
Presence/absence and total hemodialysis access thrombotic events
The presence or absence and total hemodialysis access thrombotic events (fistula and/or graft thrombosis or dialysis catheter thrombosis) will be assessed across the study duration per patient.
Time frame: 12 months
Presence/absence and total mortality
The presence or absence and total all-cause and cardiovascular cause mortality will be assessed across the study duration per patient.
Time frame: 12 months