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Trial registered on ANZCTR


Registration number
ACTRN12615000750583
Ethics application status
Approved
Date submitted
1/07/2015
Date registered
21/07/2015
Date last updated
21/07/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Calcium Intake Fracture Outcome Study
Scientific title
Effects of Calcium Supplementation on Clinical Fracture and Bone Structure: a 5-Year, Double-Blind, Placebo-Controlled Trial in Elderly Women (Calcium Intake Fracture Outcome Study)
Secondary ID [1] 286932 0
Nil
Universal Trial Number (UTN)
Trial acronym
CAIFOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 295357 0
Condition category
Condition code
Musculoskeletal 295622 295622 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Five-year, double-blind, placebo-controlled study of 1460 women recruited from the population and older than 70 years (mean age, 75 years) who were randomized to receive calcium carbonate, 600 mg twice per day, or identical placebo.
Intervention code [1] 292125 0
Prevention
Comparator / control treatment
Identical placebo tablet containing cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 295337 0
Clinical incident osteoporotic fractures

The diagnosis and classification of vertebral and nonvertebral fractures were confirmed by radiographic reports.
Timepoint [1] 295337 0
Incident fractures to 5 years
Primary outcome [2] 295338 0
Vertebral deformity

Vertebral deformities were assessed using morphometric x-ray absorptiometry software on a densitometer (software version 9.1, Hologic 4500A; Hologic Corp) at years 1 and 5. Incident vertebral deformities were defined as vertebral deformities not present at year 1, with a reduction in posterior, middle, or anterior heights of 20% or more.
Timepoint [2] 295338 0
Years 1 and 5
Primary outcome [3] 295339 0
Adverse events

Adverse events resulting in attendance to a health care professional were recorded in a diary at 4-month intervals and coded using the International Classification of Primary Care, Version 2-Plus, system database of disease coding (Family Medicine Research Unit, Department of General Practice, University of Sydney, Sydney, Australia). Adverse events were grouped according to 17 categories identified by the International Classification of Primary Care, Version 2-Plus, system.22 Atraumatic incident clinical fractures and atraumatic symptomatic vertebral fractures were reported in the diary.
Timepoint [3] 295339 0
every 4 months to 5 years
Secondary outcome [1] 315384 0
Calcaneal quantitative ultrasonography (QUS) measurements of the left foot were obtained using an ultrasound densitometer (Lunar Achilles; GE Lunar Corp, Madison, Wis) at baseline and 5 years.
Timepoint [1] 315384 0
baseline and 5 years
Secondary outcome [2] 315726 0
Dual x-ray absorptiometry (DXA) bone density was measured at the hip and whole body on a fan-beam densitometer (Hologic Acclaim 4500A; Hologic Corp, Waltham, Mass) at 1 and 5 years.
Timepoint [2] 315726 0
Year 1 and year 5
Secondary outcome [3] 315727 0
Peripheral quantitative computed tomography bone structure and density were measured in the radius at a site 4% of the length of the radius distal to the wrist joint, using a peripheral quantitative computed tomography device (XCT-2000; StraTec Medizintechnik GmbH, Pforzheim, Germany).
Timepoint [3] 315727 0
Baseline and Year 5

Eligibility
Key inclusion criteria
The key inclusion criteria was age greater than 70 years and less than or equal to 85 years, and likelihood to survive a 5-year study.
Minimum age
70 Years
Maximum age
85 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Receipt of a bone active agent.

There were no other specific exclusions so that the results could be generalized to the entire ambulant population.

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)
We recruited 1460 women during 1 year using a population-based approach in which a random selection of women (n = 24 800) older than 70 years on the electoral roll in Western Australia received a letter inviting them to join the study. Of these, 4312 individuals responded and were contacted by telephone. More than 98% of women of this age are on the electoral roll (n = 33 366).

Participants received calcium carbonate tablets, 600 mg twice per day (with morning and evening meals), or identical placebo tablets (Wyeth Consumer Healthcare, Baulkham Hills, Australia). The randomization was stratified by allocating patients to blocks according to whether a prevalent nontraumatic fracture had occurred after age 50 years, ensuring that an equal number of patients with and without a prevalent fracture received placebo or calcium.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization list was produced using a random number generator. An identification number was assigned in order by the Pharmacy Department of the Sir Charles Gairdner Hospital, Nedlands, Australia.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical procedures were performed with SPSSPC for Windows version 11.5 (SPSS, Inc, Chicago, Ill). The time to first clinical event was analyzed using the Cox proportional hazards model with and without adjustment for covariates. Differences between normally distributed characteristics of the treatment groups were determined by univariate analysis of variance with adjustments for covariates. The Mann-Whitney test was used to determine the differences between the groups for nonnormally distributed variables. All statistical tests were 2-tailed, and P<.05 was considered significant.

Power calculations were conducted before study commencement, assuming a fracture rate of 3.5% per year in the placebo group and assuming that calcium would reduce the event rate by 35%. At a power of at least 80%, at an a of .05, and allowing for a 30% noncompliance rate during the 5-year study, recruitment of 737 patients per group was required.

Recruitment
Recruitment status
Completed
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 in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 291493 0
Government body
Name [1] 291493 0
National Health and Medical Research Council of Australia
Address [1] 291493 0
GHD Building Level 1, 16 Marcus Clarke Street, Canberra ACT 2601
Country [1] 291493 0
Australia
Funding source category [2] 291579 0
Government body
Name [2] 291579 0
Healthway
Address [2] 291579 0
PO Box 1284
West Perth WA 6872
Country [2] 291579 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Hwy Crawley, WA Australia 6009
Country
Australia
Secondary sponsor category [1] 290171 0
None
Name [1] 290171 0
Address [1] 290171 0
Country [1] 290171 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293034 0
The Human Rights Committee of the University of Western Australia, Perth, Australia
Ethics committee address [1] 293034 0
35 Stirling Hwy Crawley, WA, Australia 6009
Ethics committee country [1] 293034 0
Australia
Date submitted for ethics approval [1] 293034 0
Approval date [1] 293034 0
28/11/1997
Ethics approval number [1] 293034 0
05/06/004/H50

Summary
Brief summary
Increased dietary calcium intake has been proposed as a population-based public health intervention to prevent osteoporotic fractures. We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action.

This was a five-year, double-blind, placebo-controlled study of 1460 women recruited from the population and older than 70 years (mean age, 75 years) who were randomized to receive calcium carbonate, 600 mg twice per day, or identical placebo. The primary end points included clinical incident osteoporotic fractures, vertebral deformity, and adverse events ascertained in 5 years. Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, and peripheral quantitative computed tomography of the distal radius.
Trial website
Trial related presentations / publications
Richard L. Prince; Amanda Devine; Satvinder S. Dhaliwal; Ian M. Dick. Effects of Calcium Supplementation on Clinical Fracture and Bone Structure: Results of a 5-Year, Double-blind, Placebo-Controlled Trial in Elderly Women. Archives of Internal Medicine 2006; 166(8):869-875.
Public notes

Contacts
Principal investigator
Name 58170 0
Prof Richard Prince
Address 58170 0
The University of Western Australia
35 Stirling Highway
Crawley WA 6009
Perth, Australia
Country 58170 0
Australia
Phone 58170 0
61 8 6151 0830
Fax 58170 0
Email 58170 0
Richard.Prince@uwa.edu.au
Contact person for public queries
Name 58171 0
Prof Richard Prince
Address 58171 0
The University of Western Australia
35 Stirling Highway
Crawley WA 6009
Perth, Australia
Country 58171 0
Australia
Phone 58171 0
61 8 6151 0830
Fax 58171 0
Email 58171 0
Richard.Prince@uwa.edu.au
Contact person for scientific queries
Name 58172 0
A/Prof Richard Prince
Address 58172 0
The University of Western Australia
35 Stirling Highway
Crawley WA 6009
Perth, Australia
Country 58172 0
Australia
Phone 58172 0
61 8 6151 0830
Fax 58172 0
Email 58172 0
Richard.Prince@uwa.edu.au

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