Abstract: FR-OR101
High-Dose Cholecalciferol and Clinical Outcomes in Patients Receiving Dialysis: Results of the SIMPLIFIED Trial
Session Information
- High-Impact Clinical Trials
October 23, 2026 | Location: Bluebird Ballroom, Convention Center
Abstract Time: 10:45 AM - 11:00 AM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Smith, Rona M., University of Cambridge, Cambridge, England, United Kingdom
- Cui, Molly, University of Cambridge, Cambridge, England, United Kingdom
- Caskey, Fergus, University of Bristol, Bristol, England, United Kingdom
- Chaudhry, Afzal, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom
- Cunningham, John, University College London, London, England, United Kingdom
- Humphrey, Toby, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom
- Mitra, Sandip, Manchester University NHS Foundation Trust, Manchester, England, United Kingdom
- Schoenmakers, Inez, University of East Anglia, Norwich, England, United Kingdom
- Wagner, Adam P., University of East Anglia, Norwich, England, United Kingdom
- Wheeler, David C., University College London, London, England, United Kingdom
- Wilkinson, Ian, University of Cambridge, Cambridge, England, United Kingdom
- Wilson, Edward C F, University of Exeter, Exeter, England, United Kingdom
- Yahia, Amer, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom
- Bond, Simon, University of Cambridge, Cambridge, England, United Kingdom
- Hiemstra, Thomas, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom
Group or Team Name
- On behalf of the SIMPLIFIED Investigators.
Background
Vitamin D deficiency is common in patients on dialysis and guidelines recommend cholecalciferol replacement. However, whether supplementation improves survival or major clinical outcomes remains uncertain
Methods
SIMPLIFIED was a pragmatic, multicenter, open-label trial randomizing adults on dialysis 1:1 to oral cholecalciferol 60000IU every 2 weeks or standard care (SOC). Outcomes were ascertained using routinely collected healthcare data. Primary outcome was all-cause mortality. Secondary outcomes included hospitalization for cardiovascular events, infection, fracture, and a prespecified major adverse cardiovascular event (MACE) composite comprising cardiovascular death, myocardial infarction, coronary revascularization, stroke or peripheral arterial disease
Results
A total of 3866 participants were randomized at 55 UK centers (1940 cholecalciferol; 1926 SOC). Median age was 65 years; 68% were male; 80% white. During follow-up, 883/1940 (45.5%) participants assigned cholecalciferol and 934/1926 (48.5%) assigned SOC died. Cholecalciferol did not significantly reduce all-cause mortality (HR 0.95, 95%CI 0.86-1.04; p=0.27). Prespecified subgroup analyses identified treatment-effect interactions for sex and ethnicity (both p-interaction=0.02). Among non-white participants, mortality was lower with cholecalciferol (HR 0.72, 95%CI 0.56-0.92), and among males the HR was 0.89 (95% CI 0.79-0.99)(Fig 1).
Cholecalciferol did not significantly reduce first hospitalization for the broader cardiovascular composite (HR 0.96, 95%CI 0.88-1.06; p=0.44), infection (HR 0.96, 95%CI 0.87-1.06; p=0.43), or fracture (HR 0.89, 95%CI 0.70-1.12; p=0.32). However, the prespecified MACE composite occurred less frequently with cholecalciferol (HR 0.88, 95%CI 0.78-0.99; p=0.03). Serious adverse-event rates were similar between groups
Conclusion
High-dose cholecalciferol did not significantly reduce all-cause mortality in an unselected dialysis population. The reduction in MACE and lower mortality hazard among non-white participants are hypothesis-generating findings warranting further investigation
Funding
- Government Support - Non-U.S.