The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612000270819
Ethics application status
Approved
Date submitted
5/03/2012
Date registered
6/03/2012
Date last updated
22/05/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Zoledronate and fracture prevention in early postmenopausal women
Scientific title
Efficacy of very infrequent zoledronic acid on vertebral fractures and bone mineral density in early postmenopausal women
Secondary ID [1] 280075 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 285984 0
Condition category
Condition code
Musculoskeletal 286174 286174 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Intravenous infusion of 5mg zoledronic acid at baseline and an intravenous infusion of placebo (saline solution) at 5 years. (Total of two infusions during study)
Arm 2: Intravenous infusion of 5mg zoledronic acid at baseline and 5 years. (Total of two infusions during study)
Intervention code [1] 284397 0
Prevention
Intervention code [2] 284408 0
Treatment: Drugs
Comparator / control treatment
Arm 3: Intravenous infusion of placebo (normal saline) at baseline and 5 years. (Total of two infusions during study)
Control group
Placebo

Outcomes
Primary outcome [1] 286640 0
New morphometric vertebral fractures since baseline assessed using thoracic and lumbar spine plain x-rays
Timepoint [1] 286640 0
Thoracic and spinal x-rays will be taken at baseline, 5 years, and 10 years in all participants.
Secondary outcome [1] 296346 0
Change in bone mineral density from baseline measured at the spine, hip and whole body with dual enery x-ray absorptiometry
Timepoint [1] 296346 0
Bone density will be measured at baseline, 5 years and 10 years in all participants, and in a subset of 225 participants at 2.5 years and 7.5 years.
Secondary outcome [2] 296347 0
Incidence of osteoporotic fractures assessed using plain x-rays
Timepoint [2] 296347 0
10 years
Secondary outcome [3] 296348 0
Change in bone turnover markers since baseline
Timepoint [3] 296348 0
Bone turnover markers will be measured in a subset of 225 participants at baseline, 2.5 years, 5 years, 7.5 years and 10 years
Secondary outcome [4] 296349 0
Equivalence of 5mg zoledronate administered using two different dosing intervals (either 5mg at baseline or 5mg at baseline and 5 years) in preventing new morphometric vertebral fractures since baseline assessed using thoracic and lumbar spine plain x-rays
Timepoint [4] 296349 0
Thoracic and spinal x-rays will be taken at baseline, 5 years, and 10 years in all participants.
Secondary outcome [5] 296383 0
Adverse events (including the expected adverse event of acute phase reactions)
Timepoint [5] 296383 0
Medical history and adverse events will be assessed by interview at baseline, and every 6 months until 10 years. Assessments will be at a clinic visit at baseline, 5 years and 10 years, and by phone or email contact at other timepoints.

Eligibility
Key inclusion criteria
Postmenopausal women aged 50-60 years.
Bone mineral density T score at the lumbar spine, femoral neck or total hip < 0
Minimum age
50 Years
Maximum age
60 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Bone mineral density T score <-2.5 at the total hip, femoral neck or lumbar spine.
Renal impairment (estimated glomerular filtration rate > 45 ml/min).
Untreated hypothyroidism or hyperthyroidism.
Chronic liver disease.
Concurrent major systemic illness, including malignancy.
Active major gastrointestinal disease.
Metabolic bone diseases.
Previous fragility fracture of the hip or spine.
Current or past use of bisphosphonate therapy within 12 months, or past zoledronic acid use.
Use of oral glucocorticoid drugs equivalent to an average dose of at least prednisone 2.5mg/day during the preceding 6 months.
Use of hormone replacement therapy within 12 months

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subject numbers will be allocated by personnel based in a different building and having no contact with study subjects. Infusions of study medication (zoledronate or placebo) 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)
Computer-generated random numbers in variable blocks
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
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] 4183 0
New Zealand
State/province [1] 4183 0

Funding & Sponsors
Funding source category [1] 284830 0
Government body
Name [1] 284830 0
Health Research Council of New Zealand
Address [1] 284830 0
Address: P.O. Box 5541
Wellesley St
Auckland 1141
Country [1] 284830 0
New Zealand
Primary sponsor type
Individual
Name
Dr Mark Bolland
Address
Bone and Joint Research Group,
Department of Medicine,
University of Auckland,
85 Park Road, Grafton
Private Bag 92019,
Auckland, 1142
Country
New Zealand
Secondary sponsor category [1] 283708 0
None
Name [1] 283708 0
Address [1] 283708 0
Country [1] 283708 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286819 0
Northern X Regional Ethics Committee
Ethics committee address [1] 286819 0
Private Bag 92522
Wellesley Street
Auckland 1141
Ethics committee country [1] 286819 0
New Zealand
Date submitted for ethics approval [1] 286819 0
Approval date [1] 286819 0
07/12/2011
Ethics approval number [1] 286819 0
NTX/11/11/097

Summary
Brief summary
Low bone density is a strong risk factor for fracture, but 80% of fractures occur in women without low bone density. We plan to investigate whether zoledronate, an effective osteoporosis treatment, can be given very infrequently by injection to prevent bone loss and spinal fractures in women with normal or only mildly low bone density.
The proposed study is a prospective, randomised, double-blind, placebo-controlled, trial to be carried out over a period of ten years. 1050 post-menopausal women, aged 50-60 years, will be randomly assigned to receive either infusions of zoledronate or an inactive agent (placebo) at baseline and at five years. There will be three treatment groups- women who receive zoledronate at baseline and five years, women who receive zoledronate at baseline and placebo at five years, and women who receive placebo at baseline and five years. The main outcomes are occurrence of new spinal fractures and changes in bone density. Participants will have study visits every 5 years, and phone or email visits every six months, and at baseline, five years, and 10 years, participants will have a measurement of bone density and xrays of the spine.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33866 0
A/Prof Mark Bolland
Address 33866 0
Bone and Joint Research Group, Department of Medicine, University of Auckland, 85 Park Road, Grafton Private Bag 92019, Auckland, 1142
Country 33866 0
New Zealand
Phone 33866 0
6493737599
Fax 33866 0
Email 33866 0
m.bolland@auckland.ac.nz
Contact person for public queries
Name 17113 0
Dr Dr Anne Horne
Address 17113 0
Bone and Joint Research Group,
Department of Medicine,
University of Auckland,
85 Park Road, Grafton
Private Bag 92019,
Auckland, 1142
Country 17113 0
New Zealand
Phone 17113 0
64 9 9239787
Fax 17113 0
64 9 3072865
Email 17113 0
a.horne@auckland.ac.nz
Contact person for scientific queries
Name 8041 0
A/Prof Mark Bolland
Address 8041 0
Bone and Joint Research Group,
Department of Medicine,
University of Auckland,
85 Park Road, Grafton
Private Bag 92019,
Auckland, 1142
Country 8041 0
New Zealand
Phone 8041 0
64 9 3737599
Fax 8041 0
64 9 3737677
Email 8041 0
m.bolland@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary