Vitamin K to Attenuate Coronary Artery Calcification in Hemodialysis Patients

Number of participants recruited per month at each site) and an overall crude average of each site's rate.

Proportion of prescribed doses received.

Proportion of participants who dropped out from the trial.

Proportion of participants who adhered to the study protocol.

Proportion of eligible patients consented and randomized.

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.

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.

The proportion of participants with a 10% or greater decrease in Agatston calcium scores will be assessed at study exit vs baseline.

The proportion of participants with a 10% or greater decrease in volume calcium scores will be assessed at study exit vs baseline.

The absolute and percentage change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline.

The absolute and percentage change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline.

The absolute and percentage change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline.

The absolute and percentage change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline.

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.

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.

The prevalence and incidence of thoracic vertebral fractures (anterior and lateral radiographs) will be assessed at baseline and study exit.

The prevalence and incidence of lumbar vertebral fractures (anterior and lateral radiographs) will be assessed at baseline and study exit.

The presence or absence and total hospitalizations will be assessed across the study duration per patient.

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.

The presence or absence and total thrombotic events (deep vein thrombosis and pulmonary embolism) will be assessed across the study duration per patient.

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.

The presence or absence and total all-cause and cardiovascular cause mortality will be assessed across the study duration per patient.

C-reactive protein (CRP), interleukin 6 (IL-6), leptin, insulin, glucose, homeostasis model assessment-insulin resistance (HOMA-IR) will be assessed at baseline, four months, eight months, and study exit.

Hemoglobin, albumin, Kt/V, creatinine, lipid profile (HDL, LDL, triglycerides, and total cholesterol), and parameters of mineral metabolism (phosphate, calcium, PTH, and ALP) will be assessed monthly. Serum FGF-23 will be assessed at baseline, four months, eight, and study exit.

Prescription of concomitant medications (listed below) will be assessed monthly.

• Calcium-based phosphate binders
• Non-calcium-based phosphate binders
• Calcitriol
• Vitamin D Calcimimetic
• HMG-CoA reductase inhibitors
• Angiotensin converting enzyme inhibitors
• Angiotensin II receptor blockers
• Anti-platelet therapy: acetylsalicylic acid, clopidogrel bisulfate, and dipyridamole

Average dosage and total exposure across study exit will be assessed for calcitriol, other vitamin D drugs, and calcium-based phosphate binders.

Muscle atrophy and adipose tissue will be assessed using an L3 slice (CT scan) at study exit vs. baseline. Specifically, muscle, normalized muscle, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) cross-sectional area (cm2 or cm2/m2) and muscle, IMAT, VAT and SAT radiodensity (HUs) measurements will be included.

Myoglobin, calciprotectin, neutrophil gelatinase-associated lipocalin, matrix-metalloproteinase 2, osteopontin, myeloperoxidase, serum amyloid A, insulin-like growth factor binding protein-4, intercellular adhesion molecule 1, vascular cell adhesion protein 1, matrix-metalloproteinase 9, and cystatin C will be assessed at baseline, four months, eight months and study exit.

1,25-OH-D3, 25-OH-D2, percent 25D that is D2, Total 25D, 24,25(OH)2D3, 25D3:24,25D3, 24,25D3:25D3, 3epi25-OH-D3, 3epi25-OH-D3(%), 1,25(OH)2D3, 1,24,25(OH)3D3, 1,25(OH)2D3:1,24,25(OH)3D3, 1,25(OH)2D3:1,24,25(OH)3D3 will be assessed at baseline, four months, eight months and study exit.