A pragmatic, randomised, open-label, multi-centre UK registry-facilitated trial evaluating the effect of high-dose cholecalciferol on mortality in patients on dialysis: the SIMPLIFIED trial
Abstract
Background: Vitamin D deficiency is common in patients with end stage kidney disease (ESKD) and is a strong predictor of death from cardiovascular disease, infections and cancer. Currently only 68% of patients in the UK survive 3 years or more on dialysis. Vitamin D replacement typically utilises activated (1α-hydroxylated) vitamin D compounds allowing for impaired renal activation. However, this approach increases blood calcium concentrations and may paradoxically accelerate vitamin D catabolism. Contemporary treatment guidelines recommend replacement with inactive (unhydroxylated) vitamin D3 (cholecalciferol), instead relying on autocrine and paracrine vitamin D activation in target tissues. However, the impact of this approach on clinical outcomes has not yet been tested in adequately powered trials.
Methods: The SIMPLIFIED (Survival Improvement with Cholecalciferol in Patients on Dialysis) trial will test whether supplementation with high-dose cholecalciferol improves survival. Adult dialysis patients will be recruited from one of 72 UK renal centres, by local clinicians and research nurses, and randomly assigned in a 1:1 ratio to high-dose open-label cholecalciferol or standard care, stratified by site. Trial outcomes will be captured using existing data sources including Office of National Statistics (ONS) for deaths and Hospital Episode Statistics (HES) for secondary endpoints. The primary endpoint of the trial is all-cause mortality. Key secondary endpoints include…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 4,200 participants or records.
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