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

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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

2022-06-11

2025-12-01

2025-12-01

Recruiting

Early phase I

60

Inclusion criteria: * 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 Exclusion criteria: * 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) * Of childbearing status * History of femur fracture attributed to osteoporosis medication use (i.e. midshaft femoral fracture or atypical femoral fracture) * Major dental surgery planned within the next 6 months (e.g. root canal). * Known allergy or intolerance to denosumab. * Expected to receive a parathyroidectomy for hyperparathyroidism in the next 12 months

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 60, 'type': 'ESTIMATED'}}

2024-05-14