Every year, thousands of dialysis patients in the UK are given expensive active vitamin D compounds that may actually be harming them, while a cheap, safe alternative sits on the shelf. The problem is that no one has run a large enough trial to prove the alternative works. This trial will directly compare high-dose cholecalciferol—the same inactive vitamin D found in over-the-counter supplements—against the current standard of care in 4,200 dialysis patients across all UK units. If cholecalciferol reduces deaths, it would transform a routine clinical decision that affects every single person on dialysis. The impact would be immediate and practical: a switch to a treatment that costs pennies per dose, avoids the dangerous calcium spikes caused by active vitamin D compounds, and could lower the three leading causes of death in this patient group—heart disease, infections, and cancer. Because the trial uses data already collected by the UK Renal Registry, the results will be directly relevant to NHS cost-effectiveness decisions, giving clinicians the evidence they need to change practice.
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Vitamin D deficiency is highly prevalent in patients with kidney failure and is associated with increased mortality. Kidney failure patients are treated with “active” vitamin D compounds (VDRAs) based on the now disproven belief that activation can only occur in the kidneys. VDRAs induce hypercalcaemia, result in tissue deficiency of calcitriol, and may promote vascular calcification. Contemporary treatment guidelines now recommend administration of “native” vitamin D (Cholecalciferol). This guidance is not currently implemented given the lack of evidence from randomised trials. Cholecalciferol has been used to treat vitamin D deficiency for more than 80 years. It is cheap and safe, even at high doses. In contrast, VDRAs are expensive and despite their wide use, their efficacy and safety have never been tested in interventional trials. There is an urgent unmet need for a trial to determine which approach is preferable. In this trial, we will test the hypothesis that population-wide supplementation with high-dose cholecalciferol (inactive vitamin D) patients receiving dialysis will reduce mortality and improve quality of life. DESIGN Randomised open-label registry-facilitated trial of high dose cholecalciferol versus standard care in patients receiving dialysis SETTING All UK dialysis units TARGET POPULATION Dialysis patients aged 18 years or older TECHNOLOGIES BEING ASSESSED High dose vitamin D supplementation (cholecalciferol) versus standard care. OUTCOME MEASURES All outcome measures will be captured using routinely collected data from the UK Renal Registry (UKRR) and the Health and Social Care Information Centre (HSCIC). The primary efficacy endpoint will be all-cause mortality, given that the three leading causes of death for patients on dialysis (cardiovascular, infectious and malignant disease) are all strongly associated with vitamin D deficiency and likely to be impacted by its supplementation. Secondary endpoints: 1) Hospitalisation for composite cardiovascular endpoint of CV death, acute coronary syndrome, heart failure or arrhythmia admissions, or stroke 2) Hospitalisation for infection 3) Incidence of malignancy 4) Health-related Quality of life (EQ5D, KDQoL) 5) Cost effectiveness of cholecalciferol from the perspective of the NHS. SAMPLE SIZE The study will recruit 4200 patients over 3 years. We estimate that the control arm has a 3-year survival of 68%. Using Cox proportional hazards regression (two-sided 5% significance) will enable a hazard ratio of 0.87 to be detected with 90% power assuming that 2200 events occur during the trial (estimated to require a duration of 7 years). TIMETABLE Recruitment will require 3 years. The trial will conclude once 2200 events have occurred.
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