PRevEnting FracturEs in REnal Disease 1
- Conditions
- Kidney DiseasesDialysis; ComplicationsFragility FractureChronic Kidney Disease-Mineral and Bone Disorder
- Interventions
- Other: Calcium and vitamin D prophylaxisDiagnostic Test: Monitoring of post-injection calcium and phosphate
- Registration Number
- NCT05096195
- Lead Sponsor
- Western University, Canada
- Brief 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
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Calcium and vitamin D prophylaxis 60 mg of denosumab (Prolia) will be administered every 6 months over a 15 - month period. Monitoring of serum calcium and phosphate will occur and bloodwork will be drawn for 7 weeks following each denosumab injection. Correction of vitamin D deficiency (if required), the adjustment of calcium dialysate and the provision of intravenous (IV) or oral (po) calcitriol/calcidiol will be administered as needed following each denosumab injection as described in the Beside Protocol. Once the study monitoring period is over, serum calcium monitoring and management will occur as per routine care in the dialysis centre. All intervention activities will occur during regularly scheduled hemodyalisis sessions. Intervention Monitoring of post-injection calcium and phosphate 60 mg of denosumab (Prolia) will be administered every 6 months over a 15 - month period. Monitoring of serum calcium and phosphate will occur and bloodwork will be drawn for 7 weeks following each denosumab injection. Correction of vitamin D deficiency (if required), the adjustment of calcium dialysate and the provision of intravenous (IV) or oral (po) calcitriol/calcidiol will be administered as needed following each denosumab injection as described in the Beside Protocol. Once the study monitoring period is over, serum calcium monitoring and management will occur as per routine care in the dialysis centre. All intervention activities will occur during regularly scheduled hemodyalisis sessions. Intervention Denosumab 60 mg/ml 60 mg of denosumab (Prolia) will be administered every 6 months over a 15 - month period. Monitoring of serum calcium and phosphate will occur and bloodwork will be drawn for 7 weeks following each denosumab injection. Correction of vitamin D deficiency (if required), the adjustment of calcium dialysate and the provision of intravenous (IV) or oral (po) calcitriol/calcidiol will be administered as needed following each denosumab injection as described in the Beside Protocol. Once the study monitoring period is over, serum calcium monitoring and management will occur as per routine care in the dialysis centre. All intervention activities will occur during regularly scheduled hemodyalisis sessions.
- Primary Outcome Measures
Name Time Method Recruitment rate 4 months Number or N (%) participants recruited within 4 months of trial initiation at each centre
Adherence to study intervention 15 months N(%) participants randomized to the intervention receive \>90% of their scheduled denosumab injections
Adherence to usual care 15 months N(%) participants randomized to usual care who do not receive a prescription for denosumab
- Secondary Outcome Measures
Name Time Method Median change in parathyroid hormone 4 weeks following denosumab injection Median (IQR) change in parathyroid hormone between baseline and last followup
Fragility fracture 15 months N (%) with hospital encounter for fragility fracture of the hip, vertebrae, humerus, wrist, or pelvis at 15 months
Participant satisfaction with E-Platform 15 months Mean (SD) Likert scale score (1=not satisfied, 5=very satisfied)
Participant satisfaction with E-Consent 15 months Mean (SD) Likert scale score (1=not satisfied, 5=very satisfied)
Treatment-related hypocalcemia as assessed by CTCAE v4.0 4 weeks following denosumab injection N(%) with Grade 2: albumin-adjusted serum calcium \< 2.00 to 1.75 mmol/L; Grade 3 albumin-adjusted serum calcium \< 1.75 to 1.5 mmol/L; Grade 4: albumin-adjusted serum calcium \< 1.5 mmol/L at 1, 2, 3 and 4 weeks following denosumab injection.
Mean change in serum calcium 4 weeks following denosumab injection Mean (standard deviation), change in corrected serum calcium between baseline and last followup
Median change in serum calcium 4 weeks following denosumab injection Median (interquartile range, IQR), change in corrected serum calcium between baseline and last followup
Mean change in parathyroid hormone 4 weeks following denosumab injection Mean (standard deviation) change in parathyroid hormone between baseline and last followup
Participant satisfaction with intervention 15 months Mean (SD) Likert scale score in those randomized to intervention (1=not satisfied, 5=very satisfied)
Trial Locations
- Locations (6)
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Huron Perth Healthcare Alliance - Stratford General Hospital
🇨🇦Stratford, Ontario, Canada
St. Michaels Hospital
🇨🇦Toronto, Ontario, Canada
Woodstock Hospital
🇨🇦Woodstock, Ontario, Canada