PRevEnting FracturEs in REnal Disease - 1

NCT05096195 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 3638
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

PREFERRED-1 is a pilot study designed to determine the feasibility of a large randomized, pragmatic, open-label, comparative-effectiveness trial of denosumab for the prevention of fragility fractures in people receiving hemodialysis. The pilot study will enroll at least 60 patients from across 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. Primary outcomes include recruitment feasibility and treatment adherence. Secondary outcomes include safety and participant satisfaction with our protocol and processes.

Conditions

Kidney Diseases; Dialysis; Complications; Fragility Fracture; Chronic Kidney Disease-Mineral and Bone Disorder

Keywords

Pilot Study; Fracture; denosumab; hemodialysis

Outcome Measures

Primary Outcomes (3)

• Recruitment rate

  Number or N (%) of participants randomly allocated within 26 weeks of trial initiation at each centre.

  26 weeks

• Adherence to study intervention

  Number (%) of participants randomized to the intervention who received \>90% of their scheduled treatments to study end.

  15 months

• Adherence to usual care

  Number (%) of participants randomized to usual care who received no prescription for denosumab to study end.

  15 months

Secondary Outcomes (8)

• Treatment-related hypocalcemia as assessed by CTCAE v4.0

  within 7 weeks following denosumab injection

• Mean change in serum calcium

  7 weeks following denosumab injection

• Median change in serum calcium

  7 weeks following denosumab injection

• Mean change in parathyroid hormone

  7 weeks following denosumab injection

• Median change in parathyroid hormone

  7 weeks following denosumab injection

Study Arms (2)

Intervention

EXPERIMENTAL

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.

Drug: Denosumab 60 mg/ml; Other: Calcium and vitamin D prophylaxis; Diagnostic Test: Monitoring of post-injection calcium and phosphate

Usual care

NO INTERVENTION

Usual care participants will continue to receive the typical standard of care in their dialysis unit which includes their routine dialysis monitoring and bloodwork. They will not receive denosumab, calcium and vitamin prophylaxis. There will be no extra monitoring or bloodwork.

Interventions

Denosumab 60 mg/ml DRUG

Details described in intervention arm/group description section.

Also known as: Prolia

Intervention

Calcium and vitamin D prophylaxis OTHER

Details described in intervention arm/group description section.

Intervention

Monitoring of post-injection calcium and phosphate DIAGNOSTIC_TEST

Details described in intervention arm/group description section.

Intervention

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treating nephrologist/nurse practitioner in the dialysis unit deems that a prescription for study drug (denosumab) will be safe/reasonable in the potential participant.
• Age ≥40 years
• Access to denosumab through provincial drug benefits (i.e. evidence of receiving outpatient prescription medications through the Ontario Drug Benefits Program, Ontario Disability Support Program)
• Baseline albumin-corrected serum calcium ≥2.15 mmol/L, PTH ≥15 pmol/L (or 2-9x the upper limit of normal for the local laboratory).
• High risk of fragility fracture defined by: a) ≥15% 10-year risk of major osteoporotic fracture or \>3% 10-year risk of hip fracture (using the World Health Organization's Fracture Risk Assessment Tool which is validated in hemodialysis),OR b) a prior history of hip or vertebral fracture (where the later could have been asymptomatic and only observed radiographically), OR c) two or more fragility fractures of the humerus, wrist, and/or pelvis (e.g. 2 humerus fractures, humerus and wrist fracture).43

You may not qualify if:

• Expected to recover kidney function, stop hemodialysis, pursue palliative care, or transfer to home or peritoneal dialysis within 12 months (as assessed by a health professional).
• Expected to start IV bisphosphonates (i.e. pamidronate or zoledronic acid).
• Current use of cinacalcet (Sensipar).
• Current use of an osteoporosis medication including:
• Denosumab
• Bisphosphonates
• Alendronate (Fosavance or Fosamax)
• Risedronate (Actonel or Actonel DR)
• Zoledronic acid (Aclasta) or Pamidronate
• Raloxifene (Evista)
• Oral or conjugated estrogen
• Topical, oral or injectable testosterone (Androgel, Testim, Fortesta, Androderm, testosterone enanthate and testosterone cypionate)
• Teriperatide (Forteo)
• Romosozumab (Evenity)
• Calcitonin (Calcimar)

Sponsors & Collaborators

• Western University, Canada: lead
• ICES: collaborator
• Academic Medical Organization of Southwestern Ontario: collaborator
• Western University: collaborator
• The Kidney Foundation of Canada: collaborator

Study Sites (6)

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

Huron Perth Healthcare Alliance - Stratford General Hospital

Stratford, Ontario, N5A 2Y6, Canada

Location

St. Michaels Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Woodstock Hospital

Woodstock, Ontario, N4V 0A4, Canada

Location

Related Publications (1)

• Clemens KK, Cowan A, Dixon S, Naylor K, Weir MA, Thain J, Khan T, Silver S, Molnar AO, Sultan N, Holden RM, Hiremath S, Wald R, Kitchlu A, Arnold J, Field B, Garg AX. 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. BMJ Open. 2025 Sep 10;15(9):e097195. doi: 10.1136/bmjopen-2024-097195.

  PMID: 40935429 DERIVED

MeSH Terms

Conditions

Kidney Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Fractures, Bone

Interventions

Denosumab; Calcium

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hyperparathyroidism, Secondary; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Study Officials

• Kristin K Clemens, MD, MSc

  St. Joseph's Health Care London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 27, 2021
• Study Start: June 11, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)