POS-274 A RANDOMIZED TRIAL OF EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON CVD, INFLAMMATION AND BONE METABOLISM MARKERS IN CKD: DESIGN AND METHODS

Abstract

Introduction: Short term studies have shown that vitamin D supplementation may favorably influence vascular function, inflammation and bone metabolism in CKD There are no long-term studies that have looked at hard clinical end points in this regard This study will explore the effect of cholecalciferol supplementation on cardiovascular disease, markers of inflammation and bone metabolism in CKD We present the design and results of initial pilot phase of the proposed clinical trial Methods: The study is a multicenter, prospective, randomized, placebo-controlled, double blind trial in two parallel groups After a run-in-phase of 2 weeks, the enrolled patients are randomized in 1:1 ratio to receive cholecalciferol or matching placebo Cholecalciferol is given at the dosage of 60,000 IU/2 weeks The patients will be followed up at 3, 6, 9, 12, 24 and 36 months after enrolment All clinical events and hospitalizations during the course of the study will be recorded Primary outcome is a composite of Major Adverse Cardiovascular Events (MACE) that includes new onset heart failure, coronary heart disease, peripheral vascular disease, cerebrovascular accident, any coronary or peripheral arterial revascularization procedure and death due to cardiovascular disease Secondary outcomes include all-cause mortality, need for renal replacement therapy, change in hsCRP and IL-6, change in iPTH, FGF-23, bone specific alkaline phosphatase and CTX-1 The feasibility phase is currently being run at PGIMER, Chandigarh, India Serum levels of 25(OH)D, calcium, and iPTH will be checked at every scheduled follow up visit The concurrent clinical care will continue as per prevailing standards of care We plan to enroll 1244 patients (622 in each group) across 11 centers The trial is registered at Clinical Trials Registry of India (CTRI/2019/05/019211) Results: Till date, 340 patients have been screened for enrolment 61 have been successfully randomized;their baseline samples have been collected and stored, and drugs have been dispensed to them Till now, 30 patients have completed their 3 months follow up with 6 subjects having completed 6 months follow up as well Figure 1 depicts the conduct of study so far Table 1 shows the baseline characteristics of the study population Though delayed due to ongoing COVID 19, the study has fulfilled the pre-specified feasibility criteria of recruitment of >50% eligible subjects (achieved 94 9%), recruitment rate of ≥7 subjects per month (achieved 8 7 subjects per month) and ≤25% overall subject withdrawal rate (subject withdrawal rate 10 63%) [Formula presented] [Formula presented] Conclusions: The study has achieved pre specified feasibility criteria In the multi-centric phase, the study will set the stage for testing a relatively inexpensive intervention in the form of vitamin D supplementation for CVD in CKD Conflict of Interest: The study is funded by Department of Biotechnology, Government of India under a grant to Dr Vivek Kumar (sanction order No BT/PR29764/PFN/20/1417/2018)