Survival Improvement with Cholecalciferol in Patients on Dialysis the SIMPLIFIED registry trial

Vitamin D deficiency is common in kidney failure patients, and is a strong predictor of death from cardiovascular disease, infections and cancer Dialysis patients almost all receive pre-activated vitamin D, since it used to be thought that only the kidneys activate vitamin D However, this approach increases blood calcium concentrations which may be harmful, and paradoxically makes vitamin D deficiency worse International treatment guidelines therefore now recommend that kidney patients receive inactive vitamin D (known as cholecalciferol), since we now know that every organ activates its own vitamin D as required, even in patients with kidney failure However, this is not currently used in the NHS as it has not yet been tested in a trial We will test whether supplementation with cholecalciferol increases survival in UK dialysis patients THE STUDY We will randomly assign adult UK dialysis patients to high dose cholecalciferol or standard care Instead of seeing patients for extra study visits, we will use existing data sources (the UK Renal Registry (UKRR), Hospital Episode Statistics (HES)), and death records to find out what happens to patients in the study HOW WILL WE KNOW IF CHOLECALCIFEROL WORKS? We will determine the number of deaths over time in the two groups, to establish whether cholecalciferol improves survival Whether patients are alive or dead at the end of the study will be determined from the national deaths register, and the date of death identified We will also measure any differences in survival free from cardiovascular events, infections and cancers, the three leading causes of death in those on dialysis Then, we will use questionnaires to compare the quality of life of those in the two groups Finally, we will measure whether cholecalciferol use is cost-effective from the point of view of the NHS HOW MANY PATIENTS DO WE NEED? Currently only 68% of patients survive 3 years or more on dialysis Assuming that this will be the case in the control group, we would need to witness 2200 deaths during the study to determine with a sufficient degree of certainty whether cholecalciferol improves survival We estimate that this would require the inclusion of 4200 patients, followed for a total study duration of 7 years Put differently, this trial is designed to detect whether cholecalciferol has a clinically relevant effect by saving 4 or more lives for every 100 patients treated HOW WILL WE MAKE THE STUDY AFFORDABLE? After including patients in the study, we will have no dedicated study visits In stead, we will obtain the data we need from the UKRR, HES and the deaths register We will measure the patients' quality of life by sending questionnaires by mail or by phone interview This approach will have the important benefit of keeping to a minimum the burden of trial participation on patients and their clinical teams