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Trial registered on ANZCTR


Registration number
ACTRN12609000399291
Ethics application status
Approved
Date submitted
13/05/2009
Date registered
2/06/2009
Date last updated
14/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial on the effect of zolendronic acid versus placebo on the amount of knee pain in patients with bone marrow oedema-associated knee pain.
Scientific title
Patients with bone marrow oedema-associated knee pain, randomised to zolendronic acid or placebo, assessed by the amount of knee pain after three and twelve months.
Secondary ID [1] 288320 0
Nil
Universal Trial Number (UTN)
Trial acronym
ZAP1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee Pain 4883 0
Condition category
Condition code
Musculoskeletal 237256 237256 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Once-off intravenous infusion of 5mg zolendronic acid
Intervention code [1] 236691 0
Treatment: Drugs
Comparator / control treatment
Once-off intravenous infusion of 5mg saline
Control group
Placebo

Outcomes
Primary outcome [1] 238070 0
Magnetic resonance imaging assesment of bone marrow lesions
Timepoint [1] 238070 0
6 months following the commencement of treatment
Secondary outcome [1] 242032 0
Knee pain as measured by visual analogue score and magnetic resonance imaging
Timepoint [1] 242032 0
6 months following the commencement of treatment
Secondary outcome [2] 242237 0
Knee Function, using a questionnaire: Knee injury and Osteoarthritis Outcome Score (KOOS).
Timepoint [2] 242237 0
3, 6 and 12 months following the commencement of treatment
Secondary outcome [3] 242262 0
Safety, using interview.
Timepoint [3] 242262 0
Each visit: 3, 6 and 12 months following the commencement of treatment

Eligibility
Key inclusion criteria
Knee Pain with bone marrow oedema on magnetic resonance imaging (MRI).
Minimum age
50 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any prior use of bisphosphonate preparations, except according to the washout schedule:
2 years (if use >48 weeks)
1 year (if used >8 weeks but <48 weeks)
6 months (if used >2 weeks but <8 weeks)
2 months (if used <2 weeks)
Any intravenous bisphosphonate within the prior 2 years,
History of iritis or uveitis, except due to trauma, and resolved for >2 years prior to study
Serum calcium >2.75 mmol/L (11.0 mg/dL) or <2.00 mmol/L (8.0 mg/dL)
Serum 25-hydroxyvitamin D concentrations <15 ng/L
Use of any investigational drug(s) and/or devices within 30 days prior to randomization
creatinine clearance < 35 ml/min
Metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing
A dental exam with appropriate preventative dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor hygiene)

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 recruited by newspaper advertising.
Subjects that meet the inclusion criteria and did not meet the exclusion criteria were given an MRI.
Subject with bone marrow oedema visualised on MRI are then randomised to treatment or placebo. Allocation was determined from computer generated random numbers. Staff members not involved in assessing trial patients or performing infusions will generate the random sequences and label the vials. Sticky labels with subject ID will be placed on an appropriate vial (zolendronic acid or placebo) for each patient. Allocation is therefore double blind. Vials of zolendronic acid and placebo are identical.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation by staff member naive to the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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)

Funding & Sponsors
Funding source category [1] 237082 0
Commercial sector/Industry
Name [1] 237082 0
Novartis
Address [1] 237082 0
Novartis Pharmaceuticals Australia Pty Limited
54 Waterloo Road
North Ryde NSW 2113
Country [1] 237082 0
Australia
Primary sponsor type
University
Name
Menzies Research Institue
Address
Private Bag 23
HOBART TAS 7000
Country
Australia
Secondary sponsor category [1] 4587 0
None
Name [1] 4587 0
none
Address [1] 4587 0
none
Country [1] 4587 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239183 0
Southern Tasmania Health & Medical Human Research Ethics Committee
Ethics committee address [1] 239183 0
Office of Research Services
University of Tasmania
Private Bag 01
Hobart TAS 7001
Ethics committee country [1] 239183 0
Australia
Date submitted for ethics approval [1] 239183 0
Approval date [1] 239183 0
22/12/2008
Ethics approval number [1] 239183 0
EC00198

Summary
Brief summary
Study rationale: Bone marrow oedema has recently been recognized to be a key correlate of knee pain. There is no known treatment for this problem but it is very common in those over 50 (30% of a random sample of 50-80 year olds in Hobart) (Zhai, 2006). There are no randomized trials but there is some observational evidence suggesting bisphosphonates modify this process. Firstly, they are much less common in population samples using bisphosphonates (OR 0.1) (Carbone 2004) and an open label study with IV ibandronate led to rapid resolution of hip bone marrow oedema (Ringe 2004) when natural history studies in the knee do not suggest resolution. Zoledronic acid is an attractive candidate for the treatment of this condition dues to its one off administration and potential for long term efficacy
Trial website
Trial related presentations / publications
Laslett LL, Doré DA, Quinn SJ, Boon P, Ryan E, Winzenberg TM, Jones G. Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012 Aug;71(8):1322-8.
doi: 10.1136/annrheumdis-2011-200970.
Public notes

Contacts
Principal investigator
Name 29601 0
Prof Graeme Jones
Address 29601 0
c/o Menzies Research Institute Tasmania
University of Tasmania
Private Bag 23
HOBART TAS 7000
Country 29601 0
Australia
Phone 29601 0
+61 3 6226 7700
Fax 29601 0
Email 29601 0
Graeme.Jones@utas.edu.au
Contact person for public queries
Name 12848 0
Prof Professor Graeme Jones
Address 12848 0
Private Bag 23
Hobart TAS 7001
Country 12848 0
Australia
Phone 12848 0
+61 3 6226 7700
Fax 12848 0
+61 3 6226 7764
Email 12848 0
G.Jones@utas.edu.au
Contact person for scientific queries
Name 3776 0
Prof Professor Graeme Jones
Address 3776 0
Private Bag 23
Hobart TAS 7001
Country 3776 0
Australia
Phone 3776 0
+61 3 6226 7700
Fax 3776 0
+61 3 6226 7764
Email 3776 0
G.Jones@utas.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