BASELINE CHARACTERISTICS IN THE "IPACK-HD" STUDY (INHIBIT PROGRESSION OF CORONARY ARTERY CALCIFICATION WITH VITAMIN K IN HEMODIALYSIS PATIENTS): A PHASE 2, MULTI-CENTRE, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PILOT TRIAL

Abstract Background and Aims The leading cause of mortality for patients with end-stage kidney disease (ESKD) is cardiovascular disease (CVD). This is due, in part, to vascular calcification (VC) where calcium becomes deposited within arterial walls causing narrowing of the arteries and altering their flexibility. Matrix Gla protein (MGP), a vitamin k-dependent protein, is a key local inhibitor of VC and becomes up-regulated adjacent to sites of calcification. There is a very high prevalence of vitamin K deficiency in patients across the chronic kidney disease (CKD) spectrum and vitamin K has been shown to prevent VC in experimental models. To date, no trial has examined whether vitamin K supplementation prevents the progression of coronary artery calcification in patients with ESKD, a group in which high risk has been established. The aim of the iPACK-HD pilot study is to determine whether a trial to determine whether vitamin K has a favourable effect on coronary artery calcium (CAC) scores in patients with ESKD is feasible. Method The iPACK-HD pilot trial is a phase 2 multi-centre, double-blind, randomized, placebo-controlled clinical trial conducted in three sites (Kingston, Ottawa and London) in Ontario, Canada. Adult patients with ESKD on chronic dialysis with a baseline CAC score of ≥30 Agatston units (AUs) are randomized to receive 10 mg of vitamin K1 or matching placebo administered post-hemodialysis 3x/week for a total of 12 months. Exclusions include medical conditions that require anticoagulation and a history of either coronary artery bypass, grafting or stenting. Randomization is stratified based on diabetes and study centre. Baseline CAC scores are determined by computed tomography (CT) and demographic and laboratory data at study entry are obtained by participant interview and medical chart review. Results A total of 85 participants are randomized into this trial. Baseline characteristics of trial participants are reported as mean ± SD, median [IQR], or %. The mean age is 63 ± 13 years. There are a higher proportion of males (57%) than females and whites (85%) compared to all other ethnicities. Forty-four percent of participants have diabetes and 77% have hypertension. Dialysis vintage is 0.9 [0.4,2.7] years. Most participants take calcium-based phosphate binders (89%) and over half of participants take an HMG-CoA reductase inhibitor (53%) or vitamin D (61%). Clinical laboratory values are presented in Table 1. Total median CAC and volume calcium scores are 587 [252,1416] AUs and 482 [206,1170] mm3, respectively. Sixty-five (76%) participants had a study exit CT scan performed upon completion of the study. Of 156 doses, a median of 150 [123,155] were received and 2 [1,6] were missed. Conclusion Participants in the iPACK-HD study have a high burden of calcification but are similar in baseline characteristics to the Canadian hemodialysis population. Loss to trial completion is 24%, but the most frequent reason is kidney transplantation. Adherence to study drug is very high with few reported side effects.