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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00781261




Registration number
NCT00781261
Ethics application status
Date submitted
27/10/2008
Date registered
28/10/2008
Date last updated
14/01/2013

Titles & IDs
Public title
Osteonecrosis of the Hip and Bisphosphonate Treatment
Scientific title
A Randomised Controlled Trial of Bisphosphonate Therapy in Osteonecrosis of the Hip
Secondary ID [1] 0 0
570989
Universal Trial Number (UTN)
Trial acronym
BONES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteonecrosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zoledronic Acid
Treatment: Drugs - Placebo

Placebo comparator: Control - Subjects in the control group will receive a placebo drug for a 1 year period

Active comparator: Zoledronic Acid - Subjects in this intervention group will be given 5mg Zoledronic acid as a single injection


Treatment: Drugs: Zoledronic Acid
Subjects in the intervention group B will be given 5mg Zoledronic acid as a single injection.

Treatment: Drugs: Placebo
Subjects in the control group will receive a placebo drug for a similar period
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
reducing pain and disability in the hip
Timepoint [1] 0 0
1 years
Secondary outcome [1] 0 0
reducing progression to femoral head collapse and the need for surgical intervention
Timepoint [1] 0 0
3 years

Eligibility
Key inclusion criteria
1. aged between 18-90 years,
2. symptoms of pain and disability in at least one hip joint, or
3. positive MRI findings stage I or II on the ARCO classification
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. previous hip joint surgery on the affected hip
2. severe pain and disability at rest if treating clinician has recommended surgery
3. radiographic or MRI findings suggestive for stage III and IV on the ARCO classification
4. any iv bisphosphonate within the prior 2 years or 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)
5. active primary hyperparathyroidism
6. hypothyroidism, not appropriately controlled with long-term thyroxine therapy
7. history of iritis or uveitis, except due to trauma, and resolved for > 2 years prior to study
8. self-reported history of diabetic nephropathy or retinopathy (if diabetic, Hb A1c > 10%)
9. urine dipstick greater than or equal to 2+ protein at screening
10. AST or ALT greater than twice the upper limit of normal and/or alkaline phosphatase greater than twice the upper limit of normal
11. serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL)
12. serum 25-hydroxyvitamin D concentrations < 15 ng/L m) baseline renal insufficiency (calculated creatinine clearance less than 40 mL/min and serum creatinine greater than 175 mol/L) at V1
13. a history of invasive malignancy of any organ system, treated or untreated, in the past five years; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, ductal carcinoma in-situ (DCIS), and carcinoma in-situ (CIS) of the uterine cervix
14. any candidate patient with severe dental problems or current dental infections and/or any candidate patient with recent or impending dental surgery within three months of dosing
15. women of childbearing potential not using the contraception method(s) specified in this study (specify), as well as women who are breastfeeding

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)
Methods used to generate the sequence in which subjects will be randomised (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
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2013
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital, Department of Rheumatology - Sydney
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Brisbane and Womens Hospital - Herston
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital - Adelaide
Recruitment hospital [5] 0 0
Cabrini Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - Sydney
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5011 - Adelaide
Recruitment postcode(s) [5] 0 0
3144 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novartis
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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 surface 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 established 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
https://clinicaltrials.gov/study/NCT00781261
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Philip Sambrook, Prof
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Monique Macara
Address 0 0
Country 0 0
Phone 0 0
+61294631888
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00781261