The SIMPLIFIED Registry Trial
Survival Improvement with Cholecalciferol in Patients on Dialysis.
In the United Kingdom, nearly 30,000 people receive regular dialysis and 6,000 new patients start dialysis each year. Although this is a life-saving treatment, dialysis-requiring renal failure carries a worse prognosis than most malignancies, with a mean 3-year survival of only 68%. The mean age of UK dialysis recipients is 65 years, and after 4 years on dialysis, fewer than 40% of those aged 65 and over remain alive. Those aged 60 – 69 years have 9 times the relative risk of death compared to the UK general population (2.5 for ≥ 85’s to 26 for ≤ 29’s). The three leading causes of death are cardiovascular disease, infections, and malignancy.
Patients receiving maintenance dialysis experience significant physical, emotional, mental and psychological impairments which are reflected in Health-Related Quality of Life (HRQoL) scores. Dialysis patients value improved QoL more than they do improved survival. A wide range of interventions currently employed in this population in the NHS, at considerable cost, are aimed at improving survival and quality of life, but have either failed to show any benefit (erythropoesis stimulating agents, lipid lowering, calcimimetics) or have not been adequately evaluated in randomised trials (phosphate lowering, active vitamin D sterols). There is an urgent unmet need for interventions that improve survival in patients receiving dialysis.
SIMPLIFIED is a prospective, randomised, open-label, pragmatic, multicentre registry-facilitated superiority trial of colecalciferol (also known as cholecalciferol) versus standard care in patients receiving dialysis. 72 renal units across the UK contribute data to the UK renal registry (UKRR), and it is anticipated that SIMPLIFIED will be conducted in up to 65 of these units. Approximately 4,200 subjects will be included in the trial. The primary objective of the trial is to determine the effect of colecalciferol 60,000IU fortnightly on patient survival.
Main inclusion criteria
- Have given written informed consent to participate
- Age 18 years or over
- UK Resident
- Have dialysis-requiring End-Stage Renal Disease
Main exclusion criteria
- Current treatment with high dose ( > 1,000IU/day) cholecalciferol
- Women who are pregnant / planning to become pregnant or are breastfeeding
- Persistent hypercalcaemia (corrected calcium >2.62 mmol/l on three separate and sequential occasions without precipitating cause)
- Life expectancy <6 months
- Hypersensitivity to colecalciferol or any of the excipients
- Opted out from contributing data to the UK Renal Registry (UKRR)
Funders and sponsors
Sponsors: Sponsors: Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Dr Rona Smith
Clinical Trials Coordinator: Dr Kerrie Brusby
Telephone: 01223 254472