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Trial registered on ANZCTR


Registration number
ACTRN12609000593235
Ethics application status
Approved
Date submitted
16/07/2009
Date registered
17/07/2009
Date last updated
1/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Zoledronate in fracture prevention in osteopenic postmenopausal women.
Scientific title
Efficacy of Zoledronate in fracture prevention in osteopenic postmenopausal women.
Secondary ID [1] 283756 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fractures in women with Postmenopausal osteopenia 237194 0
Condition category
Condition code
Musculoskeletal 237517 237517 0 0
Osteoporosis
Injuries and Accidents 239596 239596 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous Zoledronate 5mg/100ml infused over 15 minutes every 18 months for 6 years (4 injections at Baseline, 18,36and 54 months)
Intervention code [1] 236899 0
Treatment: Drugs
Intervention code [2] 236956 0
Prevention
Comparator / control treatment
Placebo - 100ml Saline Intravenous infusion over 15 minutes every 18 months for 6 years ( at baseline, 18, 36, and 54 months)
Control group
Placebo

Outcomes
Primary outcome [1] 238325 0
Time to first osteoporotic fracture in osteopenic postmenopausal women. Fracture assessed by verified xray reports or film.
Timepoint [1] 238325 0
at six years from randomisation
Secondary outcome [1] 244723 0
Incidence of osteoporotic fractures in osteopenic postmenopausal women. Fracture assessed by verified xray reports or film.
Timepoint [1] 244723 0
at six years from randomisation
Secondary outcome [2] 244724 0
Time to first symptomatic fracture in osteopenic postmenopausal women. Xray reports or films will be sighted to validate the fracture.
Timepoint [2] 244724 0
at six years from randomisation
Secondary outcome [3] 244725 0
Incidence of all symptomatic fractures in osteopenic postmenopausal women. Xray reports or films will be sighted to validate the fracture.
Timepoint [3] 244725 0
at six years from randomisation
Secondary outcome [4] 244726 0
The number of osteopenic postmenopausal women who experience at least one vertebral morphometric fracture during follow-up. Fracture assessed by lateral spine xrays performed as part of the study at baseline, 3 and 6 years.
Timepoint [4] 244726 0
at six years from randomisation
Secondary outcome [5] 244727 0
Incidence of vertebral morphometric fractures in osteopenic postmenopausal women. Fracture assessed by lateral spine xrays performed as part of the study at baseline, 3 and 6 years.
Timepoint [5] 244727 0
at six years from randomisation
Secondary outcome [6] 244728 0
Change in height in osteopenic postmenopausal women.
Timepoint [6] 244728 0
at six years from randomisation
Secondary outcome [7] 244729 0
All-causes mortality in osteopenic postmenopausal women.
Timepoint [7] 244729 0
at six years from randomisation
Secondary outcome [8] 244730 0
Frequency of adverse events as specified below
1. death
2. sudden death
3. myocardial infarction
4. coronary artery revascularisation
5. stroke (neurological deficit lasting more thatn 24 hours thought to have a vascular basis)
6. Transient Ischaemic Attack (neurological deficit lasting less than 24 hours thought to have a vascular basis)
7. Cancer
8. Osteonecrosis of the jaw ( defined as exposed bone in the mouth present for >8weeks)
9. Atrial fibrillation
10. The sum of 2-5
Timepoint [8] 244730 0
at six years from randomisation

Eligibility
Key inclusion criteria
Female subjects only will be studied
They must be >5years postmenopausal and aged >65 years
Life expectancy >5years
Total hip T-score <-1.0 and >-2.5 at either hip
Minimum age
65 Years
Maximum age
85 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Renal impairment (estimated Glomerular Filtration Rate <30 ml/minute)
Untreated hypo or hyperthyroidism
Active liver disease
Concurrent major systemic disease
Active malignancey (other than skin cancers) within the last 2 years or still requiring treatment (eg anti-estrogens)
Metabolic bone disease
Regular use of Hormone Replacement Therapy within the previous 1 year
Treatment with bisphosphonates in the previous 1 year
Current treatment with glucocorticoid drugs
Regular use of other bone-active drugs in the previous year
Bone Mineral Density of Lumbar spine (L1-4) <-3.0

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be randomised to receive infusions of either zoledronic acid 5mg in 100mL or this volume of normal saline over 15 minutes. Infusions will be prepared by a staff member who has no contact with the study subjects and no role in any other study procedures including assessments of end-points. All personnel having contact with study subjects and the subjects themselves will be blinded to treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatments will be allocated randomly using a minimisation algorithm balancing for age and the occurrence of fractures after the age of 40 years.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 1876 0
New Zealand
State/province [1] 1876 0

Funding & Sponsors
Funding source category [1] 237299 0
Government body
Name [1] 237299 0
The Health Research Council of New Zealand
Address [1] 237299 0
P.O. Box 5541
Wellesley St
Auckland 1141
Country [1] 237299 0
New Zealand
Primary sponsor type
Individual
Name
Professor Ian Reid
Address
Department of Medicine
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 236781 0
Individual
Name [1] 236781 0
Associate Professor Andrew Grey
Address [1] 236781 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country [1] 236781 0
New Zealand
Secondary sponsor category [2] 236782 0
Individual
Name [2] 236782 0
Dr Mark Bolland
Address [2] 236782 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country [2] 236782 0
New Zealand
Secondary sponsor category [3] 236783 0
Individual
Name [3] 236783 0
Dr Anne Horne
Address [3] 236783 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country [3] 236783 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239396 0
Northern X Regional Ethics Committee
Ethics committee address [1] 239396 0
Private Bag 92 522
Wellesley St
Auckland 1010
Ethics committee country [1] 239396 0
New Zealand
Date submitted for ethics approval [1] 239396 0
09/06/2009
Approval date [1] 239396 0
01/07/2009
Ethics approval number [1] 239396 0
NTX/09/06/054

Summary
Brief summary
This study is to determine whether the administration of the bone strengthening drug Zoledronate will reduce the numbers of fractures occurring in women who have low bone density but whose densities are not low enough to be classified as having osteoporosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29870 0
Prof Ian Reid
Address 29870 0
Department of Medicine, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1023
Country 29870 0
New Zealand
Phone 29870 0
+64 9 9236259
Fax 29870 0
+64 9 9232375
Email 29870 0
i.reid@auckland.ac.nz
Contact person for public queries
Name 13117 0
Dr Dr Anne Horne
Address 13117 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country 13117 0
New Zealand
Phone 13117 0
(64)09 9239787
Fax 13117 0
(64)09 9232375
Email 13117 0
a.horne@auckland.ac.nz
Contact person for scientific queries
Name 4045 0
Prof Professor Ian Reid
Address 4045 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
Country 4045 0
New Zealand
Phone 4045 0
(64) 09 9236259
Fax 4045 0
(64)09 9232375
Email 4045 0
i.reid@auckland.ac.nz

No information has been provided regarding IPD availability
How or where can supporting documents be obtained?
Type [1] 109 0
Study protocol
Citation [1] 109 0
Link [1] 109 0
Email [1] 109 0
Other [1] 109 0
The protocol and SAP are available as supplementary data to the NEJM paper. https://www.nejm.org/doi/full/10.1056/NEJMoa1808082
Attachment [1] 109 0
Type [2] 338 0
Study protocol
Citation [2] 338 0
Link [2] 338 0
Email [2] 338 0
Other [2] 338 0
https://www.nejm.org/doi/full/10.1056/NEJMoa1808082
Attachment [2] 338 0
Type [3] 339 0
Statistical analysis plan
Citation [3] 339 0
Link [3] 339 0
Email [3] 339 0
Other [3] 339 0
https://www.nejm.org/doi/full/10.1056/NEJMoa1808082
Attachment [3] 339 0
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary