PRevEnting FracturEs in REnal Disease-1 (PREFERRED-1): protocol for a pilot study of a pragmatic, randomised controlled trial of denosumab for the prevention of fragility fractures in haemodialysis

OBJECTIVE: Patients receiving haemodialysis are at very high risk of fragility fracture, yet there are no proven treatments for fracture prevention. We will advance a pilot study on the feasibility of a large, pragmatic, randomised controlled trial (RCT) of denosumab for fragility fracture prevention in haemodialysis. TRIAL DESIGN: PRevEnting FracturEs in REnal Disease-1 is a pragmatic, open-label, pilot study of an RCT of a denosumab care pathway embedded in routine care haemodialysis centres. METHODS: We will recruit at least 60 participants at high risk of fracture from at least 6 haemodialysis centres in Ontario, Canada. They must be aged 40 years or older, have access to provincial drug coverage, have appropriate baseline calcium and parathyroid hormone levels and be deemed suitable for denosumab by their kidney care provider. Participants will be randomised 1:1 to denosumab (with supports to mitigate hypocalcaemia) versus usual care using block randomisation by a central statistician (computer-generated sequence). Primary outcomes include recruitment feasibility and adherence. Secondary outcomes include safety (hypocalcaemia) and participant satisfaction with our protocol and processes. Study investigators and data analysts will be blind to treatment allocation.We will present results descriptively. The trial was approved by Clinical Trials Ontario and local research ethics boards across study sites. RESULTS: Primary and secondary outcomes will be published on trial completion. CONCLUSIONS: This pilot will inform the feasibility of conducting a large-scale, efficiently run, pragmatic RCT to test whether a denosumab care pathway safely reduces the risk of fragility fracture in patients receiving haemodialysis. Results have the potential to transform fracture care in real-world patients with kidney and metabolic bone disease. TRIAL REGISTRATION NUMBER: NCT05096195.