Denosumab for Broken Bones in Dialysis Patients
(PREFERRED-1 Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial examines the effectiveness of denosumab (also known as Prolia or Xgeva) in preventing bone fractures in individuals on hemodialysis. Participants will be divided into two groups: one receiving usual care and the other receiving denosumab injections every six months. The trial will assess the feasibility of organizing a larger study based on participant enrollment and retention. It is suitable for dialysis patients at high risk of bone fractures who are not currently using osteoporosis medications. As a Phase 4 trial, denosumab has already received FDA approval and proven effective, and this research aims to understand its benefits for more patients.
Will I have to stop taking my current medications?
If you are currently taking certain osteoporosis medications, including denosumab, bisphosphonates, or others listed in the trial's exclusion criteria, you will need to stop taking them to participate in this trial. The protocol does not specify a washout period, but you should discuss this with the trial team.
What is the safety track record for denosumab?
Research has shown that denosumab can pose safety concerns for people with chronic kidney disease. One study found that denosumab increases the risk of severe hypocalcemia, or very low calcium levels in the blood, particularly in those with advanced kidney problems. Another study noted that patients taking steroids or certain other medications might face a higher risk of infections when using denosumab.
However, evidence indicates that denosumab does not harm kidney function in patients with severe kidney disease, which is reassuring for those concerned about kidney health. The FDA has approved denosumab for various conditions, suggesting it is generally considered safe with proper monitoring.
Prospective trial participants should consider these risks and consult a healthcare provider to determine if denosumab is a suitable option.12345Why are researchers enthusiastic about this study treatment?
Denosumab is unique because it offers a fresh approach to treating bone issues in dialysis patients by targeting a protein called RANKL. This mechanism is different from the standard treatment options like calcium supplements and vitamin D, which mainly focus on supporting bone health indirectly. Researchers are excited about denosumab because it directly inhibits the cells that break down bone, potentially leading to stronger bones and fewer fractures in a population that is highly vulnerable to bone damage. Additionally, its administration every six months during regular dialysis sessions makes it convenient for patients.
What evidence suggests that denosumab might be an effective treatment for fragility fractures in dialysis patients?
Research has shown that denosumab can reduce the risk of bone fractures and improve bone strength in people with chronic kidney disease (CKD), including those on dialysis. One study found that denosumab reduced fracture risk by 45% compared to oral bisphosphonates, another bone-strengthening medication. In this trial, some participants will receive denosumab to assess its effectiveness in dialysis patients. However, denosumab may increase the risk of serious heart problems, so discussing the benefits and risks with a healthcare provider is crucial. Overall, denosumab is one of the approved treatments in Canada for preventing fractures in CKD patients.26789
Who Is on the Research Team?
Kristin K Clemens, MD, MSc
Principal Investigator
St. Joseph's Health Care London
Are You a Good Fit for This Trial?
This trial is for adults over 40 on outpatient maintenance hemodialysis with chronic kidney disease at high risk of bone fractures. They must have certain blood calcium, PTH, and ALP levels and be eligible for denosumab through Ontario's drug programs. Exclusions include current use of specific osteoporosis medications or treatments, planned major dental surgery, known allergy to denosumab, or expected changes in dialysis treatment within a year.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive 60 mg of denosumab every 6 months over a 15-month period, with monitoring of serum calcium and phosphate, and administration of vitamin D and calcium as needed.
Follow-up
Participants are monitored for safety and effectiveness after treatment, including monitoring of serum calcium and parathyroid hormone levels.
What Are the Treatments Tested in This Trial?
Interventions
- Denosumab
Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:
- Osteoporosis in postmenopausal women
- Bone loss associated with hormone ablation therapy for prostate cancer
- Bone loss associated with hormone ablation therapy for breast cancer
- Treatment of postmenopausal women with osteoporosis at high risk for fracture
- Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
- Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
- Treatment of osteoporosis in postmenopausal women at high risk for fracture
- Treatment to increase bone mass in men with osteoporosis at high risk for fracture
- Treatment of osteoporosis in postmenopausal women
- Treatment of bone loss associated with hormone ablation therapy for prostate cancer
Find a Clinic Near You
Who Is Running the Clinical Trial?
Western University, Canada
Lead Sponsor
ICES
Collaborator
Western University
Collaborator
ICES
Industry Sponsor
Academic Medical Organization of Southwestern Ontario
Collaborator
The Kidney Foundation of Canada
Collaborator