Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000321943
Ethics application status
Approved
Date submitted
7/02/2019
Date registered
9/03/2020
Date last updated
9/03/2020
Date data sharing statement initially provided
9/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Do bisphosphonate tablets improve bone health in patients on dialysis
Scientific title
A double blind, randomised controlled pilot study of the effect of bisphosphonates versus placebo on parameters associated with fracture risk in patients on dialysis.
Secondary ID [1] 297336 0
None
Universal Trial Number (UTN)
U1111-1228-1624
Trial acronym
Study to Assess Bone after Risedronate in ESKD
SABRE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End Stage Kidney Disease 311451 0
fracture risk 315894 0
Condition category
Condition code
Renal and Urogenital 291210 291210 0 0
Kidney disease
Musculoskeletal 314166 314166 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The bisphosphonate risedronate 35 mg (Actonel EC) or identical placebo given orally once weekly after a haemodialysis session. The tablet will be given to the patient by a staff member within 1 hour of th3e completion of the dialysis session. The duration of treatment will be 12 months from commencement of the study.
Intervention code [1] 288542 0
Treatment: Drugs
Comparator / control treatment
Matched microcellulose placebo capsule given once weekly after haemodialysis
Control group
Placebo

Outcomes
Primary outcome [1] 318981 0
change in Bone Mineral Density at the hip by DXA
Timepoint [1] 318981 0
12 months
Primary outcome [2] 322835 0
Change from baseline in the buckling ratio, which is an indicator of femoral neck instability and is calculated by the DXA software as the femoral neck radius divided by the femoral neck cortical thickness.
Timepoint [2] 322835 0
12 months
Secondary outcome [1] 366611 0
change in femoral neck cortical thickness assessed from hip DXA images using hip structural analysis
Timepoint [1] 366611 0
12 months
Secondary outcome [2] 366612 0
change in the trabecular bone score assessed from lumbar spine DXA images
Timepoint [2] 366612 0
12 months
Secondary outcome [3] 366613 0
change in cortical thickness at the calcar by hip structural analysis from DXA images
Timepoint [3] 366613 0
12 months
Secondary outcome [4] 366614 0
change in Bone Mineral Density at the lumbar spine assessed by DXA
Timepoint [4] 366614 0
12 months
Secondary outcome [5] 366615 0
change in 3D-Shaper hip cortical volume assessed from DXA images
Timepoint [5] 366615 0
12 months
Secondary outcome [6] 366616 0
change in the abdominal aortic calcification (AAC-24) score based on assessment of lateral abdominal X-rays that include the abdominal aorta.
Timepoint [6] 366616 0
12 months
Secondary outcome [7] 378919 0
incident non vertebral fracture.
For non vertebral fracture, patients are seen 3 times weekly by dialysis staff. Patients will be asked to report any incident fracture. Patients will be asked about fracture by a study coordinator, who will contact patients at 3 monthly intervals. Fractures will be confirmed from imaging studies.
Timepoint [7] 378919 0
12 months
Secondary outcome [8] 379964 0
change in Bone Mineral Density at the forearm using DXA
Timepoint [8] 379964 0
12 months
Secondary outcome [9] 379965 0
Change in cortical thickness at the femoral shaft using DXA images and hip structural analysis
Timepoint [9] 379965 0
12 months
Secondary outcome [10] 381008 0
Incident vertebral fracture
Vertebral fracture will be diagnosed using standard definitions of a reduction in vertebral height of 20% or more. An incident vertebral fracture will be diagnosed if a vertebral fracture is present on the 12 month lateral spine X-ray that was not present on the baseline lateral spine X-ray.
Timepoint [10] 381008 0
12 months

Eligibility
Key inclusion criteria
age 50 and over
Satellite haemodialysis
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Planned parathyroid surgery
Planned living related kidney transplant surgery within 12 months
Active non skin malignancy
Bilateral hip replacement making DXA hip bone mineral density impossible and hip structural analysis impossible
Gastro oesophageal reflux or gastritis or peptic ulcer disease symptoms that are not controlled with regular medications
A serum parathyroid hormone (PTH) level less than 2 times the upper normal range of the intact-PTH assay
A serum alkaline phosphatase (ALP) level below the normal lower range
Inability to provide informed consent

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)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computerised sequence generation
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
stratified for age, sex and presence of diabetes.
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary analysis will be on intention to treat basis but a per protocol analysis will also be conducted. All adverse events will be collected and analysed. Prespecified subgroup analyses will be by age 50-59, 60-69 and equal to or greater than 70 years of age, by number of comorbid conditions based on the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA): 0, 1-2 and equal to or greater than 3 and on diabetes present / presumed or absent, also recorded from ANZDATA.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2020
Actual
Date of last participant enrolment
Anticipated
1/04/2021
Actual
Date of last data collection
Anticipated
1/04/2022
Actual
Sample size
Target
114
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13066 0
Auburn Hospital & Community Health Services - Auburn
Recruitment hospital [2] 13067 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 13068 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 25573 0
2144 - Auburn
Recruitment postcode(s) [2] 25575 0
2145 - Westmead
Recruitment postcode(s) [3] 25574 0
2148 - Blacktown

Funding & Sponsors
Funding source category [1] 301899 0
Government body
Name [1] 301899 0
Western Sydney Local Health District Research and Education Network
Country [1] 301899 0
Australia
Funding source category [2] 304720 0
Commercial sector/Industry
Name [2] 304720 0
Theramex Australia Pty Ltd.,
Country [2] 304720 0
Australia
Primary sponsor type
Hospital
Name
Westmead Hospital Research and Education Network
Address
Westmead Hospital, Cnr Hawkesbury Rd, Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 301652 0
None
Name [1] 301652 0
None
Address [1] 301652 0
Country [1] 301652 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302589 0
Western Sydney Local Health District HREC
Ethics committee address [1] 302589 0
Westmead Hospital, Hawkesbury Rd. Westmead NSW 2145
Ethics committee country [1] 302589 0
Australia
Date submitted for ethics approval [1] 302589 0
13/02/2019
Approval date [1] 302589 0
07/06/2019
Ethics approval number [1] 302589 0
HREC Ref: 2 0 1 8 /ETH00734 Research Office File No: (5996)

Summary
Brief summary
We hypothesise that in patients on dialysis, with normal or elevated bone turnover, the use of bisphosphonates will improve some or all of BMD, the trabecular bone score (indicating changes to bone microarchitectural parameters), cortical parameters and the buckling ratio assessed by hip structural analysis, and 3D-Shaper hip parameters that independently assess cancellous and cortical compartments from DXA images. If improvements in these parameters are seen with bisphosphonates, a larger study with fracture outcomes is proposed
Trial website
Trial related presentations / publications
Public notes
1. Aleksova J, Milat F, Kotowicz M, Pasco J, Schultz C, Wong P, Ebeling, Elder GJ. Patients with End Stage Kidney Disease have Markedly Abnormal Cortical Hip Parameters by Dual-Energy X-ray Absorptiometry. Nephrology Dialysis Transplant 7 November 2019 gfz195, https://doi.org/10.1093/ndt/gfz195
2. Aleksova J, Kurniawan S, Elder GJ. The Trabecular Bone Score is Associated with Bone Mineral Density, Markers of Bone Turnover and Prevalent Fracture in Patients with End Stage Kidney Disease. Osteoporosis International 2018. 29(6), 1447-1455
3. Sharma AK, Toussaint ND, Masterton R, Holt SG, Rajapakse CS, Ebeling PR, Mohanty ST, Baldock P, Elder GJ. Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation. Am J Nephrol. 2018 May 23;47(6):376-384.
4. Aleksova J, Kurniawan S, Vucak-Dzumhur M, Kerr P, Ebeling PR, Milat F, Elder GJ. Aortic Vascular Calcification Is Inversely Associated With The Trabecular Bone Score In Patients Receiving Dialysis; Bone. 2018 Aug;113:118-123.
5. Lewis JR, Wong G, Taverniti A, Vucak-Dzumhur M, Elder GJ. Association between aortic calcification, cardiovascular events and mortality in kidney and pancreas-kidney transplant recipients. American Journal of Nephrology 2019 Aug 8:1-10. doi: 10.1159/000502328.

Contacts
Principal investigator
Name 45374 0
Prof Grahame Elder
Address 45374 0
Department of Renal Medicine, Westmead Hospital
Hawkesbury Rd.
Westmead
NSW 2145
Country 45374 0
Australia
Phone 45374 0
+61 288906962
Fax 45374 0
+61 2 96339351
Email 45374 0
g.elder@garvan.org.au
Contact person for public queries
Name 45375 0
Prof Grahame Elder
Address 45375 0
Department of Renal Medicine, Westmead Hospital
Hawkesbury Rd.
Westmead
NSW 2145
Country 45375 0
Australia
Phone 45375 0
+61 288906962
Fax 45375 0
+61 2 96339351
Email 45375 0
g.elder@garvan.org.au
Contact person for scientific queries
Name 45376 0
Prof Grahame Elder
Address 45376 0
Department of Renal Medicine, Westmead Hospital
Hawkesbury Rd.
Westmead
NSW 2145
Country 45376 0
Australia
Phone 45376 0
+61 288906962
Fax 45376 0
+61 2 96339351
Email 45376 0
g.elder@garvan.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Baseline and 12 month DXA bone density data by site (hip, spine and forearm), advanced hip analysis data (buckling ratio and cortical thickness), trabecular bone score data and abdominal aortic calcification score data
When will data be available (start and end dates)?
Start date: following submission of publication of the trial data. Completion of the trial is expected to be June 2022.
End date: not determined.
Available to whom?
researchers on request or if required for publication purposes.
Available for what types of analyses?
meta analysis and verification of results
How or where can data be obtained?
request to Prof Grahame Elder
g.elder@garvan.org.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
6461Ethical approval    365579-(Uploaded-06-03-2020-18-01-29)-Study-related document.pdf
6863Study protocol  penelope.murie@health.nsw.gov.au
6864Informed consent form  penelope.murie@health.nsw.gov.au
6865Statistical analysis plan  penelope.murie@health.nsw.gov.au



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.