Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000104257
Ethics application status
Approved
Date submitted
22/10/2008
Date registered
13/02/2009
Date last updated
15/08/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of bisphosphonate therapy in osteonecrosis of the hip.
Scientific title
A randomised controlled trial to study the effectiveness of potent bisphosphonate (Zoledronic Acid) therapy in patients with early osteonecrosis of the hip.
Secondary ID [1] 253217 0
BONES Study
Universal Trial Number (UTN)
Trial acronym
BONES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
osteonecrosis of the hip 3805 0
collapse femoral head 3806 0
Condition category
Condition code
Musculoskeletal 3988 3988 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to one of two groups, the intervention (zoledronic acid infusion) and control group (placebo infusion). Participants will have a 66% chance of being in the intervention group and a 33% chance of being in the control group. Subjects in the intervention group will be given 5mg Zoledronic acid (via infusion) annually for 3 doses, this means one dose a year for 3 years. Patients with low serum 25OH vitamin D will be supplemented before zoledronate administration.
Intervention code [1] 3526 0
Treatment: Drugs
Comparator / control treatment
Subjects in the control group will receive a placebo injection (5mg saline solution) for a similar period.
Control group
Placebo

Outcomes
Primary outcome [1] 4890 0
The primary outcome of this project will be the number of patients progressing to stage III or IV on the Association Research Circulation Osseous (ARCO) scale on imaging (Magnetic Resonance Imaging (MRI)) at 12 months and with an X-ray at 36 months, including the number of patients requiring surgical intervention on the affected hip.
Timepoint [1] 4890 0
Measured at 12 months and 36 months
Secondary outcome [1] 8252 0
Changes on MRI including: size of lesion and bone oedema, measured at baseline and 12 months.
Timepoint [1] 8252 0
Measured at baseline and 12 months
Secondary outcome [2] 8253 0
Disability evaluation, The Harris Hip Score (HHS) evaluated by the Rheumatologist or Orthopaedic surgeon, is a multidimensional observational assessment which contains eight items representing pain, walking function, activities of daily living, and range of motion of the hip joint. Final score ranges from 100 (no disability) to 0 (maximum disability). The HHS is an accepted test as it can detect small changes in hip function
Timepoint [2] 8253 0
Measured at baseline, 12 months and 36 months
Secondary outcome [3] 8254 0
Quality of life. Questionnaires will be used to assess quality of life (AQoL and SF36). The AQoL consists of 5 dimensions, each of which has 3 items. The SF-36 is a short-form health survey which yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
Timepoint [3] 8254 0
Measured at baseline, 12 months and 36 months
Secondary outcome [4] 8255 0
Adverse effects. Adverse effects of the treatment zoledronic acid will be obtained through open-ended questions in the questionnaire and confirmed by a checklist. A special focus will include dental side effects. All serious adverse events and pregnancies that arise during the conduct of the trial will be reported by the investigator sponsor to Novartis within 24 hours of awareness, irrespective of causality. Follow-up information related to serious adverse events and pregnancies will also be reported within 24 hours of awareness.
Timepoint [4] 8255 0
Measured at baseline, 12 months and 36 months
Secondary outcome [5] 8256 0
Direct health care costs including; visits to a health care providers, prescriptions and over the counter medication, hospitalization and interventions. Data on direct health care costs including; visits to a health care providers, prescriptions and over the counter medication, hospitalization and interventions will be collected using monthly diaries. Participants will be requested to update these diaries and return when participants attend for 12, 24 and 36 monthly follow up. Participants will be required to also include data on indirect costs due to days off work or from usual activities.
Timepoint [5] 8256 0
3 years

Eligibility
Key inclusion criteria
symptoms of pain and disability in at least one hip joint and/or positive MRI findings stage I or II on the ARCO classification
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous hip joint surgery on the affected hip and/or severe pain and disability at rest if treating clinician has recommended surgery and/or Radiographic or MRI findings suggestive for stage III and IV on the ARCO classification

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)
Potential participants who meet the eligibility criteria will be identified by their treating Rheumatologists or Orthopaedic surgeons, followed by a screening assessment conducted by the study research staff. If suitable, participants will be invited to join the study. Prior to treatment, the study research staff will perform a baseline assessment including demographic details, age, sex, duration of symptoms, medical history including prior surgery, trauma and medication use and known risk factors for osteonecrosis. Eligible participants will be allocated their treatment according to a computer-generated table of random numbers created by the study biostatistician to balance for age, sex and 2 stages of MRI severity. Treatments will then be dispensed by participating hospital pharmacies with active and placebo tablets and infusions prepared in identical packaging to maintain blinding.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer-generated table of random numbers created by the study biostatistician
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4035 0
Commercial sector/Industry
Name [1] 4035 0
Novartis
Country [1] 4035 0
Australia
Funding source category [2] 258162 0
Government body
Name [2] 258162 0
National Health and Medical Research Council
Country [2] 258162 0
Australia
Primary sponsor type
University
Name
University of Sydney/ Northern Clinical School
Address
Royal North Shore Hospital
Pacific Highway
St Leonards 2065
Country
Australia
Secondary sponsor category [1] 3628 0
None
Name [1] 3628 0
Address [1] 3628 0
Country [1] 3628 0
Secondary sponsor category [2] 3981 0
None
Name [2] 3981 0
Address [2] 3981 0
Country [2] 3981 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6120 0
Harbour Human Research Ethics Committee (HREC)
Ethics committee address [1] 6120 0
Research Office, Level 13, Kolling Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065
Ethics committee country [1] 6120 0
Australia
Date submitted for ethics approval [1] 6120 0
Approval date [1] 6120 0
21/10/2008
Ethics approval number [1] 6120 0
0806-124M

Summary
Brief summary
Osteonecrosis of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven to be challenging. Osteonecrosis means death of bone which can occur from the loss of the blood supply or some other means. Although any age group may develop osteonecrosis, most patients are between 20 and 50 years old. The most common risk factor is a history of high steroid treatment for some medical condition. The next most common associated condition is a history of high alcohol use. There are some cases of osteonecrosis that occur in patients that are otherwise completely healthy with no detectable risk factors.
In the earliest stage of the disease, x-rays appear normal and the diagnosis is made using MRI. The advanced stages of osteonecrosis begin when the dead bone starts to fail mechanically through a process of microfractures of the bone. As the disease progresses, the surace begins to collapse until, finally the integrity of the joint is destroyed. A wide range of surgical treatments with variable success rates have been proposed for the treatment of the osteonecrosis to preserve joint integrity, including core decompression, whereby the venous hypertension that ensues is lessened and revascularisation may be induced leading to bone repair. Nonsurgical treatment options are limited and usually result in a poor prognosis. Early stage disease can be treated with protected weight bearing and physiotherapy, however some studies have shown protected weight bearing to be associated with a greater than 85% rate of femoral head collapse. Unfortunately most studies indicate that the risk for disease progression is greater with nonsurgical treatment than with surgical intervention. There are no esthablished pharmaceuticals for the prevention of treatment of osteonecrosis. Evidence is increasing that the nitrogen containing bisphosphonates may be beneficial in the treatment of osteonecrosis. One bisphosphonates (alendronate) has been evaluated in 60 patients diagnosed with osteonecrosis of the hip. Recent clinical studies have shown very promising results. All patients had symptomatic improvement after one year. Although the follow up time ranged from 3 months to 5 years, only 6 patients progressed to the point of needing surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29019 0
Prof Lyn March
Address 29019 0
Department of Rheumatology
Clinical Administration 7C
Royal North Shore Hospital
Reserve Road
ST LEONARDS NSW 2065
Country 29019 0
Australia
Phone 29019 0
+61 2 9463 1890
Fax 29019 0
+61 2 9463 1077
Email 29019 0
[email protected]
Contact person for public queries
Name 12176 0
Ms Monique Macara
Address 12176 0
Department of Rheumatology
Clinical Administration 7C
Royal North Shore Hospital
Reserve Road
ST LEONARDS NSW 2065
Country 12176 0
Australia
Phone 12176 0
+61 2 9463 1888
Fax 12176 0
Email 12176 0
[email protected]
Contact person for scientific queries
Name 3104 0
Prof Lyn March
Address 3104 0
Department of Rheumatology
Clinical Administration 7C
Royal North Shore Hospital
Reserve Road
ST LEONARDS NSW 2065
Country 3104 0
Australia
Phone 3104 0
+61 2 9463 1890
Fax 3104 0
Email 3104 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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