PRevEnting FracturEs in REnal Disease 1 — PREFERRED-1  

Kidney Diseases Clinical Trial

Official title: Denosumab for the Prevention of Fragility Fractures in Hemodialysis: a Pilot Study for an Innovative, Randomized-controlled Trial, Embedded in Routine Care

Status Recruiting

Clinical Trial Summary

PREFERRED-1 is a pilot study for a large randomized, pragmatic, open-label, comparative-effectiveness trial. The pilot study will enroll at least 60 patients from at least 6 different hemodialysis centres in Ontario, Canada. Patients on outpatient maintenance hemodialysis at high risk of fragility fracture, will be randomized 1:1 to a denosumab care pathway vs. usual care

Clinical Trial Description

Despite a fragility fracture risk that is >5-fold higher than those without chronic kidney disease (CKD), there is a lack of evidence on how to prevent fracture in patients on hemodialysis. Medications known to prevent fragility fracture in other populations, are either contraindicated in dialysis, or associated with severe side effects.

Denosumab (Prolia) is one of the only Health Canada approved medications for fragility fracture prevention across the CKD stages. While small clinical trials inclusive of hemodialysis patients have noted that denosumab improves bone mineral density and reduces bone turnover, whether this treatment effectively and safely prevents fragility fracture in this population still remains unclear.

Instead of conducting an expensive traditional RCT where results might fail to apply to the "real-world", the study will embed a trial of denosumab into routine care. The intervention will be delivered by healthcare staff. Participants will be closely followed at the dialysis unit where the participant has dialysis treatments. The baseline characteristics and outcomes will be captured using repurposed data held at ICES.

The overall aim of the PREFERRED Program is to determine whether a denosumab care pathway vs. usual care (i.e., non-use of denosumab) alters the risk of fragility fracture in patients receiving in-centre hemodialysis. PREFERRED-1 is a pilot study that will inform the feasibility of conducting a large-scale, efficiently run, randomized-controlled trial in Canada to test whether denosumab reduces the risk of fragility fracture in patients receiving hemodialysis.

The objectives of PREFERRED-1 are to:

1. Prove that the streamlined methods of enrollment will facilitate patient recruitment across multiple centres in a timely way;

2. Demonstrate there is good adherence to the trial protocol and that the trial protocol was well-received by patients;

3. Ensure that participants are adherent with treatment assignment (i.e., intervention group to denosumab, minimal cross-over to denosumab in non-use group);

4. Confirm there are no 'signals' of unmanageable harm (i.e. hypocalcemia) that would prevent testing of this intervention on a larger scale.

PREFERRED-1 will be deemed a success if:

• The study can randomly allocate at least 60 patients from at least 6 hemodialysis centres within 6-months of the trial being activated at each centre.

• Demonstrate that patients randomly allocated to denosumab receive over 90% of the scheduled injections at 0, 6 and 12 months

• Patients randomly allocated to no denosumab (i.e. usual care) do not receive a prescription for denosumab.

This "high-risk" innovative pragmatically approached trial focused on better treatments for fracture prevention in those with kidney disease will

1. inform transformational change in the care of real-world patients;

2. produce essential knowledge to safely prevent fracture in patients with kidney disease, and the associated costs to the healthcare system;

3. foster the conduct of collaborative, multidisciplinary care for those with complex kidney disease. ;

Related Conditions & MeSH terms

• Bone Diseases
• Chronic Kidney Disease-Mineral and Bone Disorder
• Dialysis; Complications
• Fractures, Bone
• Fragility Fracture
• Kidney Diseases
• Renal Insufficiency, Chronic

• NCT number: NCT05096195
• Study type: Interventional
• Source: Western University, Canada
• Contact: Jennifer Arnold
• Phone: 519-685-8500
• Email: Preferred1@sjhc.london.on.ca
• Status: Recruiting
• Phase: Phase 4
• Start date: June 11, 2022
• Completion date: December 2025