RECRUITINGPhase 2INTERVENTIONAL

Bone Loss Prevention With Zoledronic Acid or Denosumab in Critically Ill Adults

Bone Loss Prevention With Zoledronic Acid or Denosumab in Critically Ill Adults - A Randomised Controlled Trial

About This Trial

The Bone Zone trial is a prospective, multi-centre, double-blind, phase II, randomised controlled trial evaluating the effect of denosumab or zoledronic acid compared to placebo on change in bone mineral density over one year in women aged 50 years or older and men aged 70 years or older requiring admission to intensive care for greater than 24 hours. 450 women aged 50 years or older and men aged 70 years or older, admitted to intensive care for greater than 24 hours will be recruited into the study from participating study centres.

Who May Be Eligible (Plain English)

Who May Qualify: - Female age ≥ 50 years or male age ≥ 70 years - Has been in the Intensive Care Unit for 2 or more calendar days and is not expected to be discharged from the Intensive Care Unit on the second day - Has required Intensive Care Unit level support (i.e. intravenous vasoactive drugs, or invasive mechanical ventilation, or non-invasive ventilation or high flow nasal oxygen at Fraction inspired Oxygen ≥0.4 and/or gas flows ≥40L/m) for a minimum cumulative duration of 6 hours - Expected to survive the current hospital admission Who Should NOT Join This Trial: - Cancer related metastatic bone disease or multiple myeloma - Paget's disease - Pregnancy - Current estimated Glomerular Filtration Rate \<30ml/min or receiving renal replacement therapy - Known contraindication to denosumab or zoledronic acid - Obvious holes in teeth or broken teeth or dental or gum infection - Known untreated hypoparathyroidism - Current treatment with anti-fracture agent (bisphosphonate, strontium or teriparatide within previous 2 years, or menopausal hormone therapy or romosozumab within previous 12-months or denosumab within previous 6 months) - Current fragility fracture of hip, spine, femur or forearm - Exceeds weight limit for BMD scan at site or unable to undertake Bone Mineral Density for any reason - International Normalised Ratio \> 3.0 or Platelet count \< 30 10\^9/L Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Female age ≥ 50 years or male age ≥ 70 years * Has been in the Intensive Care Unit for 2 or more calendar days and is not expected to be discharged from the Intensive Care Unit on the second day * Has required Intensive Care Unit level support (i.e. intravenous vasoactive drugs, or invasive mechanical ventilation, or non-invasive ventilation or high flow nasal oxygen at Fraction inspired Oxygen ≥0.4 and/or gas flows ≥40L/m) for a minimum cumulative duration of 6 hours * Expected to survive the current hospital admission Exclusion Criteria: * Cancer related metastatic bone disease or multiple myeloma * Paget's disease * Pregnancy * Current estimated Glomerular Filtration Rate \<30ml/min or receiving renal replacement therapy * Known contraindication to denosumab or zoledronic acid * Obvious holes in teeth or broken teeth or dental or gum infection * Known untreated hypoparathyroidism * Current treatment with anti-fracture agent (bisphosphonate, strontium or teriparatide within previous 2 years, or menopausal hormone therapy or romosozumab within previous 12-months or denosumab within previous 6 months) * Current fragility fracture of hip, spine, femur or forearm * Exceeds weight limit for BMD scan at site or unable to undertake Bone Mineral Density for any reason * International Normalised Ratio \> 3.0 or Platelet count \< 30 10\^9/L

Treatments Being Tested

DRUG

Denosumab 60 MG/ML

Patients allocated to the Denosumab arm will receive Denosumab 60mg in 1ml, administered via subcutaneous injection on Study Days 1 and 180.

DRUG

Zoledronic Acid 5Mg/Bag 100Ml Inj

Patients allocated to the Zoledronic acid arm will receive Zoledronic acid 5mg in 100ml 0.9% Sodium Chloride or 5% Dextrose, administered via intravenous infusion over at least 15 minutes on Study Day 1.

DRUG

Sodium Chloride 0.9% or 5% Dextrose Intravenous

Patients allocated to the placebo arm and Denosumab arm will receive 0.9% Sodium Chloride or 5% Dextrose 100ml administered via intravenous infusion over at least 15 minutes on Day 1.

DRUG

Sodium Chloride 0.9% Injection

Patients allocated to the placebo arm and Zoledronic acid arm will receive 0.9% Sodium Chloride 1ml administered via subcutaneous injection on Days 1 and Day 180

Locations (20)

St Vincent's Health Sydney

Sydney, New South Wales, Australia

Prince of Wales Hospital

Sydney, New South Wales, Australia

Blacktown Hospital

Sydney, New South Wales, Australia

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Wollongong Hospital, Illawarra Shoalhaven Health

Wollongong, New South Wales, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

The Wesley Hospital

Brisbane, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Barwon Health, University Hospital Geelong

Geelong, Victoria, Australia

Alfred Health