Protocol summary and statistical analysis plan for the bone loss prevention with zoledronic acid or denosumab in
Neil Orford1,2,3, Ary Serpa Neto3,4,5,6, Priya Nair7,8
1University Hospital Geelong, Barwon Health, Geelong, Victoria, Australia.
Background:
Older critically ill women and men experience accelerated bone loss, an increased risk of fragility fracture, and the associated burden of impaired quality of life and increased risk of death. Antiresorptive therapies are commonly used, safe, and effective in preventing bone loss in ambulatory patients. There is insufficient evidence for their routine use during recovery from critical illness.
Objective:
The objective of this study was to describe the trial protocol and statistical analysis plan for Bone Loss Prevention with Zoledronic Acid or Denosumab in Critically Ill Adults (BONE ZONE) trial.
Design Setting Participants And Intervention:
A phase IIb, multicentre, prospective, investigator-initiated, double-blind, placebo-controlled, randomised trial, with a target sample size of 330 participants. Women aged 50 years or older and men aged 70 years or older recovering from critical illness are randomly assigned to receive zoledronic acid, denosumab, or placebo in a 1:1:1 ratio.
Main Outcome Measures:
The primary outcome is annualised change in femoral neck bone mineral density in the year after intensive care unit discharge. Secondary outcomes include change in lumbar spine bone mineral density, fracture incidence, falls, hospital readmissions, mortality, safety outcomes, and quality of life. All analyses will be conducted on an intention to treat basis.
Conclusion:
The BONE ZONE trial will evaluate the efficacy and safety of antiresorptive medication administered during recovery from critical illness to patients at higher risk of bone loss and provide robust evidence to inform the need and design for a phase III trial.
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